560:
sequential manner – Thr432 is phosphorylated first, followed by Ser431. Phosphorylation of the Ser431 residue drives a significant conformational change in the KaiC hexamer. The CI and CII rings of the protein complex stack more tightly, exposing the previously occluded B-loop. The B-loop in turn recruits KaiB, which simultaneously binds to KaiA and KaiC. KaiB binding removes KaiA from the A-loop, and in turn both promotes the autophosphatase activity of KaiC and inhibits its autokinase activity. Dephosphorylation of KaiC occurs in the subjective night, and proceeds in the reverse order of phosphorylation; Thr432 is dephosphorylated before Ser431.
593:
interacting with KaiC. The KaiB tetramer exists in equilibrium with a monomeric form of the protein. However, monomeric KaiB must undergo a radical change in tertiary structure to associate with KaiC, shifting from a so-called ground state conformation (gs-KaiB) to a fold-switched conformation (fs-KaiB) capable of binding to the KaiC B-loop. To date, KaiB is the only known metamorphic clock protein – a class of proteins capable of reversible fold-switching.
625:
mechanisms rely on biochemical changes that track photosynthetic reactions performed by the cyanobacterium, reactions that exhibit rate increases proportional to ambient light intensity. CikA and LdpA, for example, sense the redox state of the intracellular environment and relay changes to the Kai oscillator. In addition, KaiA and KaiC appear to directly detect metabolites of photosynthesis – specifically quinone and
568:
597:
the B-loop first becomes exposed - until dusk. As a result, phospho-RpaA accumulates as the day progresses and peaks near dusk, appropriately timing increases in the expression of Class 1 genes. Moreover, this time-lag in KaiB binding delays the onset of autophosphatase activity in KaiC, contributing to the circadian period of the cyanobacterial oscillator.
642:. Additionally, they hope to discover the adaptive significance of circadian rhythms using clock gene mutants of cyanobacteria. The Rust lab is researching how the interactions of proteins, neurotransmitters, and ion gradients produce the behavior of living cyanobacteria cells, using a combination of techniques such as advanced biochemical
621:– whose transcript and protein levels oscillate considerable over the course of the day - constitute an operon under the control of a single promoter and are transcribed as a polycistronic mRNA. By contrast, protein levels of KaiA, which lies under the control of an independent promoter, remain fairly across a 24-hour period.
556:
are collectively referred to as the CI and CII rings. KaiC has both intrinsic autokinase and autophosphate activity, each of which can be modulated by KaiA and KaiB binding. In particular, the phosphorylation and dephosphorylation of residues Ser431 and Thr432 in the CII ring drive circadian rhythms in the Kai oscillator.
555:
KaiC is organized as a ring-shaped homohexamer. Each monomer component contains four essential structural motifs: a CI domain, a CII domain, a B-loop binding domain, and a tail that protrudes from the C-terminus known as the A-loop. Because the CI and CII domains are aligned in the KaiC hexamer, they
352:
Cyanobacteria are a group of photosynthetic, nitrogen-fixing bacteria that are known to be one of the first life forms on Earth, and are thought to have emerged at least 3,500 million years ago (Mya). They are the only known oxidative photosynthetic prokaryotes. Cyanobacteria use circadian clocks to
637:
Both Dr. Carl
Johnson’s lab at Vanderbilt University and Dr. Michael Rust’s lab at the University of Chicago have research efforts focused on the KaiABC complex. The Johnson lab, in collaboration with Dr. Hassane Mchaourab’s lab, focuses on using biophysical methods to explain how the cyanobacteria
596:
Fs-KaiB has a thioredoxin-like fold that closely resembles the N-terminus of SasA, and competitively displaces the kinase’s binding to KaiC. However, the conformation change from gs-KaiB to fs-KaiB occurs slowly, permitting SasA binding to KaiC and downstream activation of RpaA from midday – when
559:
At the start of the subjective day, the Ser431 and Thr432 residues of the KaiC hexamer are unphosphorylated, and the A-loop domains of its constituent monomers are exposed. KaiA binds to the A-loop domain of KaiC, promoting autokinase activity. Phosphorylation of the protein occurs in an ordered,
588:
SasA can bind to the exposed B-loop of the KaiC molecule upon phosphorylation of the Ser431 residue. This interaction drives SasA autophosphorylation and subsequent phosphotransfer to RpaA. Phospho-RpaA activates the expression of dusking-peaking (Class 1) genes and represses the expression of
329:
mRNA accumulation using a transcription or translation inhibitor did not prevent the circadian cycling of kaiC phosphorylation. Thus, it is the case that cyanobacterial clock rhythmicity is independent of both transcription and translation. Additionally, experiments were conducted to test the
624:
In addition, the phase of the Kai oscillator can be shifted in response to environmental changes. However, unlike phase-shifting mechanisms characterized in eukaryotic organisms, photopigments do not appear to play a role in entrainment of the cyanobacterial clock. Instead, identified input
592:
KaiB serves as a major regulator of the SasA-RpaA pathway, and exhibits structural adaptations that both contribute to circadian rhythm generation and facilitate interaction with SasA and KaiC. The majority of KaiB expressed in cyanobacteria exists as an inactive homotetramer, incapable of
186:
species. Moreover, characterization of the cyanobacterial clock demonstrated the existence of transcription-independent, post-translational mechanisms of rhythm generation, challenging the universality of the transcription-translation feedback loop model of circadian rhythmicity.
589:
dawn-peaking (Class 2) genes. Conversely, unphosphorylated RpaA represses the expression of Class 1 genes. As a result, rhythmic phosphorylation of the transcription factor, driven by the Kai oscillator and associated SasA activity, produces rhythmic patterns in gene expression.
563:
Ultimately, these circadian rhythms in KaiC phosphorylation governed by KaiA and KaiB binding create a post-translation oscillator that can interact with both input pathways to entrain to changing environmental conditions and output pathways to mediate transcriptional events.
353:
regulate nitrogen-fixation, cell division, and other metabolic processes. The vast majority of cyanobacterial genes are expressed in a circadian fashion, generally falling into Class I (dusk-peaking) and Class II (dawn-peaking) categories depending on their specific function.
543:
genes, regulates global patterns of gene expression and governs essential cellular processes including photosynthesis and cell division. Cyclic, sequential rhythms of KaiC phosphorylation and dephosphorylation constitute the oscillator’s timekeeping mechanism both
211:
rule" stipulated that cellular functions could only be coupled to a circadian oscillator in cells dividing only as fast as once in a 24-hour period. Prokaryotes, which often undergo cellular division multiple times in a single day, failed to meet this condition.
580:
Though the Kai oscillator is capable of generating endogenous rhythms in phosphorylation, it does not directly influence gene expression; none of the Kai proteins possess DNA-binding domains. Instead, a two-component system consisting of SasA, a
1227:
Holtzendorff J, Partensky F, Mella D, Lennon JF, Hess WR, Garczarek L (June 2008). "Genome streamlining results in loss of robustness of the circadian clock in the marine cyanobacterium
Prochlorococcus marinus PCC 9511".
234:
cyanobacteria, demonstrating circadian rhythmicity in a prokaryotic species. Following these discoveries, chronobiologists set out to identify the molecular mechanisms governing operation of the cyanobacterial clock.
227:
observed in cyanobacteria suggested the existence of some mechanism of circadian control. Finally, in 1986 Tan-Chi Huang and colleagues discovered and characterized robust, 24-hour rhythms of nitrogen fixation in
298:. Examination of rescue patterns in over 50 clock mutants showing either short periods, long periods or arrhythmia revealed restoration to WT phenotype in all mutants. Further sequencing revealed 19 total
356:
The rhythmic expression of cyanobacterial genes is driven by oscillation in the phosphorylation state of the Kai oscillator and its interaction with various output mechanisms. The evolution of the three
943:
Ishiura M, Kutsuna S, Aoki S, Iwasaki H, Andersson CR, Tanabe A, Golden SS, Johnson CH, Kondo T (September 1998). "Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria".
334:
gene cluster. By incubating KaiC together with KaiA and KaiB, as well as ATP, the temperature compensation aspect of the KaiABC clock was proved. Additionally, such circadian periods seen in kaiC
203:- endogenous, entrainable oscillations in biological processes with periods that roughly correspond to the 24-hour day – were once believed to be an exclusive property of eukaryotic lifeforms.
1044:
Nakajima M, Imai K, Ito H, Nishiwaki T, Murayama Y, Iwasaki H, Oyama T, Kondo T (April 2005). "Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro".
274:
in a plasmid vector allowed testing for “rescue clones” with a normal period of 25 hours. When the DNA library from this rescued clone was placed into a plasmid at the original site,
571:
Cyclic rhythms in phosphorylation of the KaiC hexamer serve as a timekeeping mechanism for the cyanobacterial Kai oscillator. Circles shaded red represent phosphorylated residues.
314:. The mutant phenotypes being all caused by a single amino acid substitution on one of the aforementioned genes determined that Kai proteins play a significant role in the
514:
are coincident - have been tentatively implicated in rudimentary timekeeping mechanisms. Others play roles in strikingly divergent cellular processes, such as the
432:
demonstrate oscillations in gene expression and cell cycle progression, but these rhythms are not self-sustaining and rapidly disappear under constant conditions.
1544:
Chang YG, Cohen SE, Phong C, Myers WK, Kim YI, Tseng R, Lin J, Zhang L, Boyd JS, Lee Y, Kang S, Lee D, Li S, Britt RD, Rust MJ, Golden SS, LiWang A (July 2015).
629:– and adjust the phase of the oscillator accordingly. To date, KaiB has not been implicated in an input pathway capable of entraining the cyanobacterial clock.
80:
68:
115:
765:
Mitsui A, Kumazawa S, Takahashi A, Ikemoto H, Cao S, Arai T (1986). "Strategy by which nitrogen-fixing unicellular cyanobacteria grow photoautotrophically".
1312:
Loza-Correa M, Sahr T, Rolando M, Daniels C, Petit P, Skarina T, Gomez Valero L, Dervins-Ravault D, Honoré N, Savchenko A, Buchrieser C (February 2014).
207:
were thought to lack the cellular complexity to maintain persistent, temperature-compensated timekeeping. In addition, the widely supported "circadian-
178:, KaiB plays a central role in operation of the cyanobacterial circadian clock. Discovery of the Kai genes marked the first-ever identification of a
321:
Initially, it was thought that a transcription-translation feedback loop was necessary in creating circadian rhythms so it was believed that
61:
1314:"The Legionella pneumophila kai operon is implicated in stress response and confers fitness in competitive environments"
714:
Kippert F (1987). "Endocytobiotic coordination, intracellular calcium signaling, and the origin of endogenous rhythms".
655:
1412:"Nucleotide binding and autophosphorylation of the clock protein KaiC as a circadian timing process of cyanobacteria"
1479:"A KaiC-associating SasA-RpaA two-component regulatory system as a major circadian timing mediator in cyanobacteria"
216:
1854:
1849:
1603:"In vitro regulation of circadian phosphorylation rhythm of cyanobacterial clock protein KaiC by KaiA and KaiB"
282:, was found to be rhythmic in nature when the fragment of the plasmid responsible for rescue was sequenced.
38:
1546:"Circadian rhythms. A protein fold switch joins the circadian oscillator to clock output in cyanobacteria"
626:
467:. The function this expanded set of clock genes remains speculative, but current evidence suggests these
1817:"Carl Johnson Laboratory." Carl Johnson Laboratory. Vanderbilt University, 2017. Web. 30 Apr. 2017. <
585:, and RpaA, a transcription factor, connect changes in KaiC phosphorylation to transcriptional events.
1644:"KaiB functions as an attenuator of KaiC phosphorylation in the cyanobacterial circadian clock system"
613:. For example, a stoichiometric ratio of clock components must be maintained to preserve rhythmicity.
1774:
1707:
1557:
1490:
1423:
1325:
1115:
1053:
1000:
953:
774:
723:
1763:"Light-driven changes in energy metabolism directly entrain the cyanobacterial circadian oscillator"
330:
self-sustainable oscillation of KaiC phosphorylation, which is important in the regulation of the
1725:
1508:
1441:
1253:
1133:
1077:
1026:
790:
747:
215:
Over time, mounting evidence began to challenge this assertion and supported the existence of a
1800:
1743:
1673:
1624:
1583:
1526:
1459:
1392:
1351:
1294:
1245:
1209:
1151:
1069:
1018:
969:
925:
876:
739:
224:
200:
1830:"Research." Rust Lab. Institute of Genomics and Systems Biology, n.d. Web. 30 Apr. 2017. <
1790:
1782:
1733:
1715:
1663:
1655:
1614:
1573:
1565:
1516:
1498:
1477:
Takai N, Nakajima M, Oyama T, Kito R, Sugita C, Sugita M, Kondo T, Iwasaki H (August 2006).
1449:
1431:
1382:
1341:
1333:
1284:
1237:
1199:
1191:
1141:
1123:
1061:
1008:
961:
915:
907:
866:
858:
825:
782:
731:
660:
582:
408:
genes are independently required for sustained circadian rhythmicity in cyanobacteria, the
1371:"Visualizing a circadian clock protein: crystal structure of KaiC and functional insights"
690:
251:
135:
1778:
1711:
1561:
1494:
1427:
1329:
1273:"Rhythmic gene expression in a purple photosynthetic bacterium, Rhodobacter sphaeroides"
1119:
1057:
1004:
957:
778:
727:
1795:
1762:
1738:
1695:
1578:
1545:
1521:
1478:
1346:
1313:
1204:
1179:
920:
895:
871:
846:
830:
809:
735:
499:
220:
167:
1668:
1643:
1146:
1103:
325:
would have this function as well. However, it was later discovered that inhibition of
1843:
1696:"Quinone sensing by the circadian input kinase of the cyanobacterial circadian clock"
1454:
1411:
695:
670:
665:
230:
1081:
751:
412:
gene is restricted to a group of higher-order cyanobacteria. For example, while the
1257:
1030:
989:"No transcription-translation feedback in circadian rhythm of KaiC phosphorylation"
794:
247:
1619:
1602:
1289:
1272:
965:
373:– remains an area of active study. Recent phylogenetic evidence suggests that the
1387:
1370:
85:
73:
685:
271:
243:
204:
183:
145:
1700:
Proceedings of the
National Academy of Sciences of the United States of America
1483:
Proceedings of the
National Academy of Sciences of the United States of America
1416:
Proceedings of the
National Academy of Sciences of the United States of America
1108:
Proceedings of the
National Academy of Sciences of the United States of America
643:
567:
255:
109:
92:
1241:
397:
into an operon under the control of a single promoter occurred shortly after
1831:
1786:
1720:
1569:
1503:
1337:
1128:
1065:
1013:
988:
503:
208:
179:
1804:
1747:
1677:
1659:
1628:
1587:
1530:
1463:
1396:
1355:
1298:
1249:
1213:
1155:
1073:
1022:
929:
880:
1436:
1195:
973:
743:
468:
340:
266:
cyanobacteria. The transformation of a 44 hour long-period clock mutant,
97:
1818:
1729:
1512:
862:
1137:
911:
495:
1445:
1369:
Pattanayek R, Wang J, Mori T, Xu Y, Johnson CH, Egli M (August 2004).
786:
162:
56:
609:, the clock is subject to various additional levels of regulation
566:
680:
675:
605:
While rhythmicity in the KaiABC oscillator can be reconstituted
175:
171:
1104:"Origin and evolution of circadian clock genes in prokaryotes"
896:"Circadian Rhythm in Amino Acid Uptake by Synechococcus RF-1"
531:
The core cyanobacterial circadian oscillator, encoded by the
278:
was found to be completely rescued. One single gene cluster,
471:
help to fine-tune a central circadian rhythm established by
1410:
Nishiwaki T, Iwasaki H, Ishiura M, Kondo T (January 2000).
847:"Circadian Rhythm of the Prokaryote Synechococcus sp. RF-1"
502:. Likely originating from lateral transfer, some of these
987:
Tomita J, Nakajima M, Kondo T, Iwasaki H (January 2005).
1694:
Ivleva NB, Gao T, LiWang AC, Golden SS (November 2006).
1642:
Kitayama Y, Iwasaki H, Nishiwaki T, Kondo T (May 2003).
894:
Chen TH, Chen TL, Hung LM, Huang TC (September 1991).
262:
to monitor the activity of this clock gene found in
141:
131:
126:
108:
103:
91:
79:
67:
55:
47:
33:
28:
23:
845:Huang TC, Tu J, Chow TJ, Chen TH (February 1990).
1173:
1171:
1169:
1167:
1165:
1102:Dvornyk V, Vinogradova O, Nevo E (March 2003).
302:specific mutants, 14 of which had mutations in
219:. For example, discrete temporal separation of
1761:Rust MJ, Golden SS, O'Shea EK (January 2011).
494:genes have been identified in some species of
389:most recently around 1,000 Mya. The fusion of
258:, a reporter for gene expression, on the gene
808:Grobbelaar N, Huang T, Lin H, Chow T (1986).
8:
435:Contrasting cyanobacterial species lacking
420:cyanobacterial genera are closely related,
1184:Microbiology and Molecular Biology Reviews
716:Annals of the New York Academy of Sciences
160:is a gene located in the highly-conserved
123:
1832:http://rustlab.uchicago.edu/research.html
1794:
1737:
1719:
1667:
1618:
1601:Nakajima M, Ito H, Kondo T (March 2010).
1577:
1520:
1502:
1453:
1435:
1386:
1345:
1288:
1203:
1145:
1127:
1097:
1095:
1093:
1091:
1012:
919:
870:
829:
576:Circadian outputs and KaiB fold switching
1689:
1687:
810:"Dinitrogen-fixing endogenous rhythm in
706:
286:is composed of three individual genes:
1271:Min H, Guo H, Xiong J (January 2005).
254:, and their colleagues used bacterial
20:
1819:https://as.vanderbilt.edu/johnsonlab/
1178:Cohen SE, Golden SS (December 2015).
518:oxidative and salt stress responses.
239:Discovery of the cyanobacterial clock
7:
1180:"Circadian Rhythms in Cyanobacteria"
16:Gene found in various cyanobacteria
831:10.1111/j.1574-6968.1986.tb01788.x
736:10.1111/j.1749-6632.1987.tb40631.x
14:
601:Regulation of the Kai oscillator
428:species. Cyanobacteria lacking
506:– particularly in cases where
385:between 3,500-2,3200 Mya, and
338:mutants were also observed in
270:, with wild-type (WT) genomic
1:
1620:10.1016/j.febslet.2010.01.016
1290:10.1016/j.febslet.2005.01.003
1230:Journal of Biological Rhythms
966:10.1126/science.281.5382.1519
401:’s appearance in the genome.
196:Prokaryotic circadian rhythms
1388:10.1016/j.molcel.2004.07.013
377:genes emerged sequentially:
656:Bacterial circadian rhythms
646:and mathematical modeling.
527:Role in the circadian clock
443:family express paralogs of
439:genes, some members of the
1871:
1318:Environmental Microbiology
217:bacterial circadian rhythm
818:FEMS Microbiology Letters
122:
1242:10.1177/0748730408316040
166:gene cluster of various
1787:10.1126/science.1197243
1721:10.1073/pnas.0606639103
1570:10.1126/science.1260031
1504:10.1073/pnas.0602955103
1338:10.1111/1462-2920.12223
1129:10.1073/pnas.0130099100
1066:10.1126/science.1108451
1014:10.1126/science.1102540
40:Synechococcus elongatus
572:
516:Legionella pneumophila
1437:10.1073/pnas.97.1.495
1196:10.1128/MMBR.00036-15
570:
1660:10.1093/emboj/cdg212
348:Evolutionary history
246:, Masahiro Ishiura,
170:species. Along with
1779:2011Sci...331..220R
1712:2006PNAS..10317468I
1562:2015Sci...349..324C
1495:2006PNAS..10312109T
1428:2000PNAS...97..495N
1330:2014EnvMi..16..359L
1120:2003PNAS..100.2495D
1058:2005Sci...308..414N
1005:2005Sci...307..251T
958:1998Sci...281.1519I
863:10.1104/pp.92.2.531
779:1986Natur.323..720M
728:1987NYASA.503..476K
912:10.1104/pp.97.1.55
573:
381:nearly 3,800 Mya,
952:(5382): 1519–23.
638:clock oscillates
318:circadian clock.
225:nitrogen fixation
201:Circadian rhythms
155:
154:
151:
150:
116:X: 2.58 - 2.59 Mb
1862:
1855:Prokaryote genes
1850:Circadian rhythm
1835:
1828:
1822:
1815:
1809:
1808:
1798:
1758:
1752:
1751:
1741:
1723:
1706:(46): 17468–73.
1691:
1682:
1681:
1671:
1648:The EMBO Journal
1639:
1633:
1632:
1622:
1598:
1592:
1591:
1581:
1541:
1535:
1534:
1524:
1506:
1489:(32): 12109–14.
1474:
1468:
1467:
1457:
1439:
1407:
1401:
1400:
1390:
1366:
1360:
1359:
1349:
1309:
1303:
1302:
1292:
1268:
1262:
1261:
1224:
1218:
1217:
1207:
1175:
1160:
1159:
1149:
1131:
1099:
1086:
1085:
1041:
1035:
1034:
1016:
984:
978:
977:
940:
934:
933:
923:
900:Plant Physiology
891:
885:
884:
874:
851:Plant Physiology
842:
836:
835:
833:
805:
799:
798:
787:10.1038/323720a0
762:
756:
755:
711:
661:Circadian rhythm
633:Current research
583:histidine kinase
404:While all three
182:oscillator in a
124:
43:
21:
1870:
1869:
1865:
1864:
1863:
1861:
1860:
1859:
1840:
1839:
1838:
1829:
1825:
1816:
1812:
1773:(6014): 220–3.
1760:
1759:
1755:
1693:
1692:
1685:
1641:
1640:
1636:
1600:
1599:
1595:
1556:(6245): 324–8.
1543:
1542:
1538:
1476:
1475:
1471:
1409:
1408:
1404:
1368:
1367:
1363:
1311:
1310:
1306:
1270:
1269:
1265:
1226:
1225:
1221:
1177:
1176:
1163:
1114:(5): 2495–500.
1101:
1100:
1089:
1052:(5720): 414–5.
1043:
1042:
1038:
999:(5707): 251–4.
986:
985:
981:
942:
941:
937:
893:
892:
888:
844:
843:
839:
807:
806:
802:
773:(6090): 720–2.
764:
763:
759:
713:
712:
708:
704:
691:Phosphorylation
652:
635:
603:
578:
529:
524:
451:referred to as
426:Prochlorococcus
418:Prochlorococcus
350:
241:
198:
193:
37:
17:
12:
11:
5:
1868:
1866:
1858:
1857:
1852:
1842:
1841:
1837:
1836:
1823:
1810:
1753:
1683:
1654:(9): 2127–34.
1634:
1613:(5): 898–902.
1593:
1536:
1469:
1402:
1375:Molecular Cell
1361:
1304:
1263:
1219:
1161:
1087:
1036:
979:
935:
886:
837:
800:
757:
705:
703:
700:
699:
698:
693:
688:
683:
678:
673:
668:
663:
658:
651:
648:
634:
631:
602:
599:
577:
574:
528:
525:
523:
520:
500:Pseudomonadota
349:
346:
240:
237:
221:photosynthesis
197:
194:
192:
189:
168:cyanobacterial
153:
152:
149:
148:
143:
139:
138:
133:
129:
128:
120:
119:
112:
106:
105:
101:
100:
95:
89:
88:
83:
77:
76:
71:
65:
64:
59:
53:
52:
49:
45:
44:
35:
31:
30:
26:
25:
15:
13:
10:
9:
6:
4:
3:
2:
1867:
1856:
1853:
1851:
1848:
1847:
1845:
1833:
1827:
1824:
1820:
1814:
1811:
1806:
1802:
1797:
1792:
1788:
1784:
1780:
1776:
1772:
1768:
1764:
1757:
1754:
1749:
1745:
1740:
1735:
1731:
1727:
1722:
1717:
1713:
1709:
1705:
1701:
1697:
1690:
1688:
1684:
1679:
1675:
1670:
1665:
1661:
1657:
1653:
1649:
1645:
1638:
1635:
1630:
1626:
1621:
1616:
1612:
1608:
1604:
1597:
1594:
1589:
1585:
1580:
1575:
1571:
1567:
1563:
1559:
1555:
1551:
1547:
1540:
1537:
1532:
1528:
1523:
1518:
1514:
1510:
1505:
1500:
1496:
1492:
1488:
1484:
1480:
1473:
1470:
1465:
1461:
1456:
1451:
1447:
1443:
1438:
1433:
1429:
1425:
1421:
1417:
1413:
1406:
1403:
1398:
1394:
1389:
1384:
1381:(3): 375–88.
1380:
1376:
1372:
1365:
1362:
1357:
1353:
1348:
1343:
1339:
1335:
1331:
1327:
1324:(2): 359–81.
1323:
1319:
1315:
1308:
1305:
1300:
1296:
1291:
1286:
1283:(3): 808–12.
1282:
1278:
1274:
1267:
1264:
1259:
1255:
1251:
1247:
1243:
1239:
1236:(3): 187–99.
1235:
1231:
1223:
1220:
1215:
1211:
1206:
1201:
1197:
1193:
1190:(4): 373–85.
1189:
1185:
1181:
1174:
1172:
1170:
1168:
1166:
1162:
1157:
1153:
1148:
1143:
1139:
1135:
1130:
1125:
1121:
1117:
1113:
1109:
1105:
1098:
1096:
1094:
1092:
1088:
1083:
1079:
1075:
1071:
1067:
1063:
1059:
1055:
1051:
1047:
1040:
1037:
1032:
1028:
1024:
1020:
1015:
1010:
1006:
1002:
998:
994:
990:
983:
980:
975:
971:
967:
963:
959:
955:
951:
947:
939:
936:
931:
927:
922:
917:
913:
909:
905:
901:
897:
890:
887:
882:
878:
873:
868:
864:
860:
856:
852:
848:
841:
838:
832:
827:
823:
819:
815:
813:
812:Synechococcus
804:
801:
796:
792:
788:
784:
780:
776:
772:
768:
761:
758:
753:
749:
745:
741:
737:
733:
729:
725:
722:(1): 476–95.
721:
717:
710:
707:
701:
697:
696:Synechococcus
694:
692:
689:
687:
684:
682:
679:
677:
674:
672:
671:Cyanobacteria
669:
667:
666:Chronobiology
664:
662:
659:
657:
654:
653:
649:
647:
645:
641:
632:
630:
628:
622:
620:
616:
612:
608:
600:
598:
594:
590:
586:
584:
575:
569:
565:
561:
557:
553:
551:
547:
542:
538:
534:
526:
521:
519:
517:
513:
509:
505:
501:
497:
493:
489:
486:Orthologs of
484:
482:
478:
474:
470:
466:
462:
458:
454:
450:
446:
442:
441:Synechococcus
438:
433:
431:
427:
424:is absent in
423:
419:
415:
414:Synechococcus
411:
407:
402:
400:
396:
392:
388:
384:
380:
376:
372:
368:
364:
360:
354:
347:
345:
343:
342:
337:
333:
328:
324:
319:
317:
316:Synechococcus
313:
309:
305:
301:
297:
293:
289:
285:
281:
277:
273:
269:
265:
264:Synechococcus
261:
257:
253:
249:
245:
238:
236:
233:
232:
231:Synechococcus
226:
222:
218:
213:
210:
206:
202:
195:
190:
188:
185:
181:
177:
173:
169:
165:
164:
159:
147:
144:
140:
137:
134:
130:
125:
121:
118:
117:
113:
111:
107:
102:
99:
96:
94:
90:
87:
84:
82:
81:RefSeq (Prot)
78:
75:
72:
70:
69:RefSeq (mRNA)
66:
63:
60:
58:
54:
50:
46:
42:
41:
36:
32:
27:
22:
19:
1826:
1813:
1770:
1766:
1756:
1703:
1699:
1651:
1647:
1637:
1610:
1607:FEBS Letters
1606:
1596:
1553:
1549:
1539:
1486:
1482:
1472:
1422:(1): 495–9.
1419:
1415:
1405:
1378:
1374:
1364:
1321:
1317:
1307:
1280:
1277:FEBS Letters
1276:
1266:
1233:
1229:
1222:
1187:
1183:
1111:
1107:
1049:
1045:
1039:
996:
992:
982:
949:
945:
938:
903:
899:
889:
857:(2): 531–3.
854:
850:
840:
824:(2): 173–7.
821:
817:
811:
803:
770:
766:
760:
719:
715:
709:
639:
636:
623:
618:
614:
610:
606:
604:
595:
591:
587:
579:
562:
558:
554:
549:
545:
540:
536:
532:
530:
515:
511:
507:
491:
487:
485:
480:
476:
472:
464:
460:
456:
452:
448:
444:
440:
436:
434:
429:
425:
421:
417:
413:
409:
405:
403:
398:
394:
390:
386:
382:
378:
374:
370:
366:
362:
358:
355:
351:
339:
335:
331:
326:
322:
320:
315:
311:
307:
303:
299:
295:
291:
287:
283:
279:
275:
267:
263:
259:
252:Carl Johnson
248:Susan Golden
242:
229:
214:
199:
161:
157:
156:
114:
39:
18:
906:(1): 55–9.
686:Oscillation
310:, and 2 in
272:DNA library
244:Takao Kondo
205:Prokaryotes
184:prokaryotic
136:Swiss-model
29:Identifiers
1844:Categories
702:References
644:microscopy
256:luciferase
132:Structures
127:Search for
110:Chromosome
104:Other data
504:orthologs
344:strains.
209:infradian
191:Discovery
180:circadian
86:NP_525056
74:NM_080317
1805:21233390
1748:17088557
1730:30052455
1678:12727879
1629:20079736
1588:26113641
1531:16882723
1513:30051673
1464:10618446
1397:15304218
1356:23957615
1299:15670851
1250:18487411
1214:26335718
1156:12604787
1082:24833877
1074:15831759
1023:15550625
930:16668415
881:16667309
752:42743872
650:See also
640:in vitro
607:in vitro
550:in vitro
522:Function
469:paralogs
361:genes –
341:in vitro
146:InterPro
34:Organism
1796:3309039
1775:Bibcode
1767:Science
1739:1859952
1708:Bibcode
1579:4506712
1558:Bibcode
1550:Science
1522:1832256
1491:Bibcode
1424:Bibcode
1347:4113418
1326:Bibcode
1258:2741470
1205:4557074
1138:3139556
1116:Bibcode
1054:Bibcode
1046:Science
1031:9447128
1001:Bibcode
993:Science
974:9727980
954:Bibcode
946:Science
921:1080963
872:1062325
795:4235387
775:Bibcode
744:3304083
724:Bibcode
611:in vivo
546:in vivo
496:Archaea
336:in vivo
306:, 3 in
142:Domains
93:UniProt
1803:
1793:
1746:
1736:
1728:
1676:
1669:156084
1666:
1627:
1586:
1576:
1529:
1519:
1511:
1462:
1452:
1446:121818
1444:
1395:
1354:
1344:
1297:
1256:
1248:
1212:
1202:
1154:
1147:151369
1144:
1136:
1080:
1072:
1029:
1021:
972:
928:
918:
879:
869:
793:
767:Nature
750:
742:
539:, and
479:, and
463:, and
369:, and
332:kaiABC
323:kaiABC
300:kaiABC
294:, and
284:kaiABC
280:kaiABC
163:kaiABC
98:P07663
57:Entrez
48:Symbol
1726:JSTOR
1509:JSTOR
1455:26691
1442:JSTOR
1254:S2CID
1134:JSTOR
1078:S2CID
1027:S2CID
814:RF-1"
791:S2CID
748:S2CID
481:kaiC1
477:kaiB1
465:kaiB3
461:kaiC3
457:kaiB2
453:kaiC2
327:kaiBC
260:psbAI
62:31251
1834:>
1821:>
1801:PMID
1744:PMID
1674:PMID
1625:PMID
1584:PMID
1527:PMID
1460:PMID
1393:PMID
1352:PMID
1295:PMID
1246:PMID
1210:PMID
1152:PMID
1070:PMID
1019:PMID
970:PMID
926:PMID
877:PMID
740:PMID
681:KaiA
676:KaiC
619:kaiC
617:and
615:kaiB
548:and
541:kaiC
537:kaiB
533:kaiA
512:kaiC
510:and
508:kaiB
498:and
492:kaiC
490:and
488:kaiB
473:kaiA
449:kaiC
447:and
445:kaiB
430:kaiA
422:kaiA
416:and
410:kaiA
399:kaiB
395:kaiB
393:and
391:kaiC
387:kaiA
383:kaiB
379:kaiC
371:kaiC
367:kaiB
363:kaiA
312:kaiB
308:kaiA
304:kaiC
296:kaiC
292:kaiB
288:kaiA
276:C44a
268:C44a
223:and
176:KaiC
174:and
172:KaiA
158:KaiB
51:kaiB
24:KaiB
1791:PMC
1783:doi
1771:331
1734:PMC
1716:doi
1704:103
1664:PMC
1656:doi
1615:doi
1611:584
1574:PMC
1566:doi
1554:349
1517:PMC
1499:doi
1487:103
1450:PMC
1432:doi
1383:doi
1342:PMC
1334:doi
1285:doi
1281:579
1238:doi
1200:PMC
1192:doi
1142:PMC
1124:doi
1112:100
1062:doi
1050:308
1009:doi
997:307
962:doi
950:281
916:PMC
908:doi
867:PMC
859:doi
826:doi
783:doi
771:323
732:doi
720:503
627:ATP
437:kai
406:kai
375:kai
359:kai
1846::
1799:.
1789:.
1781:.
1769:.
1765:.
1742:.
1732:.
1724:.
1714:.
1702:.
1698:.
1686:^
1672:.
1662:.
1652:22
1650:.
1646:.
1623:.
1609:.
1605:.
1582:.
1572:.
1564:.
1552:.
1548:.
1525:.
1515:.
1507:.
1497:.
1485:.
1481:.
1458:.
1448:.
1440:.
1430:.
1420:97
1418:.
1414:.
1391:.
1379:15
1377:.
1373:.
1350:.
1340:.
1332:.
1322:16
1320:.
1316:.
1293:.
1279:.
1275:.
1252:.
1244:.
1234:23
1232:.
1208:.
1198:.
1188:79
1186:.
1182:.
1164:^
1150:.
1140:.
1132:.
1122:.
1110:.
1106:.
1090:^
1076:.
1068:.
1060:.
1048:.
1025:.
1017:.
1007:.
995:.
991:.
968:.
960:.
948:.
924:.
914:.
904:97
902:.
898:.
875:.
865:.
855:92
853:.
849:.
822:37
820:.
816:.
789:.
781:.
769:.
746:.
738:.
730:.
718:.
552:.
535:,
483:.
475:,
459:,
455:,
365:,
290:,
250:,
1807:.
1785::
1777::
1750:.
1718::
1710::
1680:.
1658::
1631:.
1617::
1590:.
1568::
1560::
1533:.
1501::
1493::
1466:.
1434::
1426::
1399:.
1385::
1358:.
1336::
1328::
1301:.
1287::
1260:.
1240::
1216:.
1194::
1158:.
1126::
1118::
1084:.
1064::
1056::
1033:.
1011::
1003::
976:.
964::
956::
932:.
910::
883:.
861::
834:.
828::
797:.
785::
777::
754:.
734::
726::
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.