331:
774:
482:. After the PER and TIM proteins accumulate in the cytoplasm and bind together, the PER-TIM complex translocates to the nucleus. The TIM protein in these complexes mediate the accumulation of the dimeric PER-TIM protein complex and their subsequent importation into the nucleus, where the PER protein in these complexes then mediates the release of CYC-CLK from the chromatin, repressing CYC-CLK dependent transcription. Thus, CLK and CYC act as positive factors and PER and TIM as negative factors. CYC also plays a role in the
37:
728:
gene expression has been discovered in a variety of cell types and tissues including the adult head, adult eye, larval/adult central nervous system, adult crop, adult midgut, adult hindgut, larval/adult
Malpighian tubules, larval/adult fat body, adult salivary gland, adult female reproductive system,
576:
that male
Drosophila do not possess. However, to fully understand these processes, work must be done to identify downstream interactions of CYCLE proteins. In addition, similar findings have been found in mice deficient in BMAL1, the mammalian ortholog of CYC, but without the sexual dimorphism
931:
expression was rhythmic in long day (16L:8D), constant darkness, and short day (10L:14D) cycles after investigating its expression patterns in larvae brains. Further, it was found that photoperiodic conditions affect the expression patterns and/or amplitudes of this gene. In
921:, or commonly known as the Mediterranean corn borer, has been cloned in a recent study; this SnCYC was found to have 667 amino acids. Further structural analysis showed that it also contains a BCTR domain in its C-terminal in addition to the common domains found in
560:(wild-type). On average, Drosophila with no copies died after 48 days, Drosophila with one copy died after 52 days, and Drosophila with two copies died after 60 days. The premature deaths are accounted for by poor sleep in the absence of two functioning
535:
is involved with the genetic basis of other behaviors that relate to circadian processes, such as sleep, which is important for survival, as sleep deprivation can cause death in
Drosophila. There is significant correlation between having functioning
548:, which in turn play a role in regulating duration and quality of sleep. Without proper regulation of sleep, Drosophila may become sleep deprived and die. In male Drosophila, three strains were bred, one containing no copies of functioning
950:
this gene does not oscillate or change in expression patterns in response to photoperiod, therefore suggesting that this species may be useful in further studying the molecular control of circadian and photoperiodic clocks in insects.
736:
has largely focused on the role of circadian rhythmicity in other processes. In 2012, it was reported that aging reduces transcriptional oscillations of core clock genes in the fly head including cycle. Wild type
529:
between CYC-CLK and CWO lead to control of E-box mediated transcription. Some findings suggest that CWO preferentially aids in the termination of CYC-CLK mediated transcription during late night.
662:
arrhythmic mutant in one fly line because it shows arrhythmic locomotor activity patterns when a fly has 2 mutant chromosomes number 3. These mutant flies were also found to display arrhythmic
1539:
Hendricks JC, Lu S, Kume K, Yin JC, Yang Z, Sehgal A (February 2003). "Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in
Drosophila melanogaster".
2002:
Kontogiannatos D, Gkouvitsas T, Kourti A (March 2017). "The expression of the clock gene cycle has rhythmic pattern and is affected by photoperiod in the moth
Sesamia nonagrioides".
888:
creatures retain a functionally and structurally similar protein. Unlike dipterans, however, these animals have two different orthologs of the cycle gene most likely caused by a
1393:, Staknis D, Gekakis N, Steeves TD, Weitz CJ, Takahashi JS, Kay SA (June 1998). "Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim".
943:
gene is associated with diapause. This is due to the fact that under short day (diapause conditions) the photoperiodic signal alters the accumulation of mRNA. However, in
494:
cycle, allowing fluctuations in gene expression according to environmental cues. This cycle is called the transcription-translation feedback loop as demonstrated in this
584:
is also involved in
Drosophila's responses to starvation, which also directly affect life span. Starvation in Drosophila potently suppresses sleep, suggesting that the
596:
act during starvation to modulate the conflict of whether flies sleep or search for food, thus playing a critical role for proper sleep suppression during starvation.
1222:
518:. Regulation thus occurs primarily through the negative feedback by the PER-TIM protein complex in the transcription-translation feedback loop described above.
137:
1436:
Matsumoto A, Ukai-Tadenuma M, Yamada RG, Houl J, Uno KD, Kasukawa T, Dauwalder B, Itoh TQ, Takahashi K, Ueda R, Hardin PE, Tanimura T, Ueda HR (July 2007).
2033:
Shaw PJ, Tononi G, Greenspan RJ, Robinson DF (May 2002). "Stress response genes protect against lethal effects of sleep deprivation in
Drosophila".
1582:
Shaw PJ, Tononi G, Greenspan RJ, Robinson DF (May 2002). "Stress response genes protect against lethal effects of sleep deprivation in
Drosophila".
214:
757:
still maintained a normal diet response without circadian rhythmicity. Future work focusing on understanding the role of circadian rhythms in
900:
responsible for the autoregulatory transcription translation negative feedback loops (above), which are responsible for generating molecular
525:
protein in such a way that increases the robustness in the generation of high amplitude oscillations. CWO is a transcriptional repressor and
102:
90:
719:
428:
745:
in the morning, and it was recently found that lowering levels of these proteins can affect neuronal signaling. Research from 2012 on
1285:"CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless"
638:
transcription was regulated rhythmically was not fully understood. They published the papers reporting the discovery of CYCLE and
506:
is expressed constitutively (continuously) in
Drosophila cells and is present in native Drosophila tissue culture cells, unlike
2252:
83:
2247:
1980:
219:
1839:"Balance of activity between LN(v)s and glutamatergic dorsal clock neurons promotes robust circadian rhythms in Drosophila"
446:
is primarily known for its role in the genetic transcription-translation feedback loop that generates circadian rhythms in
1438:"A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock"
238:
540:
and longevity. Though the exact mechanism of this correlation is not known, it is suspected that it is due primarily to
847:
1741:"A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless"
226:
627:
1024:, although they were more resistant than other clock mutants to various stressors. Unlike other clock mutants,
893:
711:
451:
400:
1334:"Cytoplasmic interaction with CYCLE promotes the post-translational processing of the circadian CLOCK protein"
483:
858:
function, and transcription factor activity. Other non-arthropods containing the functional ortholog of the
60:
698:
mutant. This suggests that Cycle is part of the biological clock with its phenotype similar to that of the
1013:
231:
2186:"Circadian clocks in antennal neurons are necessary and sufficient for olfaction rhythms in Drosophila"
330:
495:
375:
is expressed in a variety of cell types in a circadian manner. It is involved in controlling both the
1888:"Re-patterning sleep architecture in Drosophila through gustatory perception and nutritional quality"
1487:"Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component"
1390:
1091:
572:
knocked out. This suggests female
Drosophila may have other mechanisms to compensate for a lack of
969:
945:
923:
793:
779:
355:
722:(BMAL1), and that it likely binds to Clock to activate transcription of circadian rhythm genes.
1056:
526:
19:
2135:"Differential regulation of circadian pacemaker output by separate clock genes in Drosophila"
284:
1028:
flies showed a reduced expression of heat-shock genes after sleep loss. However, activating
2197:
2042:
1695:
1591:
1402:
1345:
1129:
934:
917:
897:
471:
396:
486:
of CLK in the cytoplasm. These four proteins of the feedback loop are later degraded by a
308:
288:
157:
8:
1101:
855:
623:
2201:
2046:
1699:
1595:
1406:
1349:
522:
2223:
2115:
2066:
1962:
1914:
1887:
1863:
1838:
1814:
1789:
1770:
1716:
1683:
1659:
1634:
1615:
1564:
1511:
1486:
1462:
1437:
1371:
1314:
1029:
773:
746:
545:
1757:
1740:
1301:
1284:
2215:
2166:
2161:
2134:
2107:
2102:
2085:
2058:
2015:
2004:
Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
1954:
1919:
1868:
1819:
1762:
1721:
1664:
1607:
1556:
1516:
1467:
1418:
1363:
1306:
1021:
568:, as female Drosophila showed no significant shortening in life span even when their
565:
388:
2227:
2119:
1568:
1375:
1318:
255:
2205:
2156:
2146:
2097:
2070:
2050:
2007:
1966:
1946:
1909:
1899:
1858:
1850:
1809:
1801:
1774:
1752:
1711:
1703:
1654:
1646:
1619:
1599:
1548:
1506:
1498:
1457:
1449:
1410:
1353:
1296:
1164:
1020:
mutants showed a disproportionately large sleep rebound and died after 10 hours of
901:
889:
877:
687:
671:
647:
376:
279:
107:
95:
1983:. National Center for Biotechnology Information, U.S. National Library of Medicine
1414:
1358:
1333:
1203:. National Center for Biotechnology Information, U.S. National Library of Medicine
905:
1904:
1854:
1805:
1175:
1096:
1051:
protein. In each case, the mutation was the result of a nonsense mutation in the
635:
619:
615:
491:
479:
467:
450:. In the cell nucleus, the CYCLE protein (CYC) forms a heterodimer with a second
384:
36:
1682:
Keene AC, Duboué ER, McDonald DM, Dus M, Suh GS, Waddell S, Blau J (July 2010).
415:
totaling 1,625 base pairs which code for 413 aminos acid residues. Currently 19
318:
167:
2139:
Proceedings of the National Academy of Sciences of the United States of America
2011:
643:
610:
2210:
2185:
1950:
1937:
Wang H (May 2009). "Comparative genomic analysis of teleost fish BMAL genes".
1707:
1251:
2241:
1552:
1169:
1144:
1048:
742:
654:
flies and screening for altered locomotor activity rhythms. From the screen,
631:
487:
475:
463:
2133:
Park JH, Helfrich-Förster C, Lee G, Liu L, Rosbash M, Hall JC (March 2000).
2219:
2170:
2151:
2111:
2062:
2019:
1958:
1923:
1872:
1823:
1725:
1668:
1611:
1560:
1520:
1471:
1367:
1082:
mutation is a dominant-negative mutation which blocks the ability of CYCLE-
667:
1788:
Rakshit K, Krishnan N, Guzik EM, Pyza E, Giebultowicz JM (February 2012).
1766:
1422:
1310:
1196:
1135:
Fifteen other mutant alleles are known, but are less commonly researched.
45:. The protein sequence information was obtained from the UniProt database.
993:
974:
585:
267:
119:
1790:"Effects of aging on the molecular circadian oscillations in Drosophila"
1502:
1453:
1047:
is a recessive mutant, characterized by a severe reduction in levels of
1052:
1008:
998:
885:
873:
851:
807:
715:
404:
262:
131:
114:
1485:
Kadener S, Stoleru D, McDonald M, Nawathean P, Rosbash M (July 2007).
334:
Visual representation of CYC-CLK complex interaction with PER and TIM.
1132:
insertion. No information about the phenotype is publicly available.
881:
823:
812:
802:
798:
750:
679:
659:
424:
380:
2184:
Tanoue S, Krishnan P, Krishnan B, Dryer SE, Hardin PE (April 2004).
2054:
1650:
1603:
1684:"Clock and cycle limit starvation-induced sleep loss in Drosophila"
1388:
1121:
816:
706:
mutant showed reduced mRNA levels of both proteins. Cloning of the
663:
431:(ARNTL) and Aryl hydrocarbon receptor nuclear translocator-like 2 (
1006:
mutant does not produce a functional CYCLE protein. The resulting
588:
regulated behaviors of feeding and sleep are integrated in flies.
502:
is a clock gene and plays a role in setting and keeping rhythms, c
960:
651:
416:
360:
1435:
395:
gene is located on the left arm of chromosome 3 and codes for a
243:
1484:
1283:
Rutila JE, Suri V, Le M, So WV, Rosbash M, Hall JC (May 1998).
1063:
mutant was arrhythmic and nearly continuously active. Both the
869:
827:
819:
432:
250:
78:
2001:
1837:
Collins B, Kane EA, Reeves DC, Akabas MH, Blau J (May 2012).
1159:
1154:
1149:
1087:
1083:
865:
831:
666:. Because the mutants displayed no circadian rhythms and the
639:
459:
455:
196:
42:
1059:. Under both light-dark and continuous dark conditions, the
2183:
2032:
1581:
412:
350:
41:
The approximate 3D structure of CYC protein generated with
2132:
1739:
Allada R, White NE, So WV, Hall JC, Rosbash M (May 1998).
1197:"cyc cycle [Drosophila melanogaster (fruit fly)]"
1122:
Bloomington Drosophila Stock Center at Indiana University
702:
mutant. Assaying PER and TIM transcription levels in the
1787:
1836:
1635:"The circadian clock and pathology of the ageing brain"
904:. For a more complete list of ARNTL homologs visit the
1681:
646:. They found both genes as a result of a technique of
427:
performing the same function in other species include
1100:. The mutation is the result of a 15 to 17 base pair
604:
The identification, characterization, and cloning of
1885:
1632:
182:
aryl hydrocarbon receptor nuclear translocator-like
1538:
892:event. Much like CYCLE, the ARNTL proteins have a
2086:"Neurobiology of the fruit fly's circadian clock"
1738:
977:and engineered by researchers in the laboratory.
630:. Prior to its discovery, the mechanism by which
498:by the Howard Hughes Medical Institution. Though
2239:
2083:
850:. In each case, the orthologs retain functional
1331:
846:gene can either be found in chromosome 3 or in
729:adult male accessory gland, and adult carcass.
1282:
753:found that circadian clock mutants, including
626:along with first author Joan E. Rutila at the
1278:
1276:
1274:
1272:
1270:
1268:
1266:
556:and one containing two copies of functioning
458:(CLK). This CYC-CLK protein complex binds to
2177:
2126:
2026:
1930:
1879:
1830:
1781:
1055:found in 1999 following a forward screen of
1732:
1325:
544:playing a role in regulating expression of
1633:Kondratova AA, Kondratov RV (March 2012).
1382:
1263:
1246:
1244:
1071:mutants were identified by the same team.
720:basic helix-loop-helix ARNT-like protein 1
462:elements in promoter regions of the genes
429:basic helix-loop-helix ARNT-like protein 1
35:
2209:
2160:
2150:
2101:
1913:
1903:
1886:Linford NJ, Chan TP, Pletcher SD (2012).
1862:
1813:
1756:
1715:
1658:
1510:
1461:
1357:
1300:
927:CYC. Researchers found that the mRNAs of
1012:exhibits arrhythmic activity and cannot
772:
718:(bHLH-PAS) protein related to mammalian
329:
1332:Maurer C, Hung HC, Weber F (May 2009).
1241:
768:
552:one containing one copy of functioning
2240:
710:gene revealed that it encodes a novel
690:because of the similarity between the
805:including other members of the genus
741:show low activity of the CLOCK/CYCLE
1936:
1534:
1532:
1530:
564:. This effect, however, did display
521:The CYC-CLK also interacts with the
1128:mutant strain is the result of a p-
682:. These data also suggest that the
474:in the translation of the proteins
13:
1258:. The Genetics Society of America.
906:ARNTL species distribution article
848:scaffold/matrix attachment regions
14:
2264:
2084:Helfrich-Förster C (March 2005).
1527:
1032:before sleep deprivation rescued
765:role in maintaining rhythmicity.
694:mutant phenotype and that of the
2103:10.1111/j.1601-183X.2004.00092.x
1223:"Transcript: cyc-RA FBtr0074924"
1120:mutant strain is available from
387:by promoting transcription in a
2077:
1995:
1973:
1675:
1626:
1575:
1036:flies from its lethal effects.
628:Howard Hughes Medical Institute
1478:
1429:
1389:Darlington TK, Wager-Smith K,
1215:
1189:
973:, and most of these have been
838:, functional orthologs of the
411:gene is divided into 5 coding
1:
2253:Drosophila melanogaster genes
1758:10.1016/S0092-8674(00)81440-3
1541:Journal of Biological Rhythms
1415:10.1126/science.280.5369.1599
1359:10.1016/j.febslet.2009.04.013
1302:10.1016/S0092-8674(00)81441-5
1256:FlyBase Gene Report: Dmel/cyc
1182:
1057:ethyl methanesulfonatemutants
959:There are currently 19 known
761:will continue to investigate
484:post-translational regulation
2248:Genes on human chromosome 11
1905:10.1371/journal.pgen.1002668
1855:10.1016/j.neuron.2012.02.034
1806:10.3109/07420528.2011.635237
1639:Nature Reviews. Neuroscience
954:
896:and a PAS domain containing
608:was reported in May 1998 in
599:
7:
1794:Chronobiology International
1138:
1111:
438:
10:
2269:
2012:10.1016/j.cbpb.2017.03.003
1086:complexes from activating
996:allele. This means that a
17:
2211:10.1016/j.cub.2004.04.009
2090:Genes, Brain and Behavior
1951:10.1007/s10709-008-9328-9
1708:10.1016/j.cub.2010.05.029
1260:|accessdate=10 April 2013
1016:to any light-dark cycle.
577:exhibited by drosophila.
314:
304:
299:
295:
278:
273:
261:
249:
237:
225:
213:
203:
191:
186:
181:
163:
153:
148:
144:
130:
125:
113:
101:
89:
77:
67:
55:
50:
34:
27:
1553:10.1177/0748730402239673
1039:
980:
527:antagonistic competition
1491:Genes & Development
1442:Genes & Development
1074:
1002:with two copies of the
970:Drosophila melanogaster
915:gene found in the moth
794:Drosophila melanogaster
780:Drosophila melanogaster
674:, they determined that
359:that encodes the CYCLE
356:Drosophila melanogaster
61:Drosophila melanogaster
2152:10.1073/pnas.070036197
894:basic helix–loop–helix
834:. In other members of
784:
712:basic helix–loop–helix
523:Clockwork Orange (CWO)
401:basic helix–loop–helix
335:
20:Cycle (disambiguation)
898:transcription factors
776:
670:flies displayed long
642:in the same issue of
333:
1130:transposable element
935:Sesamia nonagrioides
918:Sesamia nonagrioides
769:Species distribution
686:gene is part of the
658:was identified as a
472:transcription factor
403:(bHLH) domain and a
397:transcription factor
138:3L: 19.81 - 19.81 Mb
18:For other uses, see
2202:2004CBio...14..638T
2047:2002Natur.417..287S
1700:2010CBio...20.1209K
1596:2002Natur.417..287S
1503:10.1101/gad.1552607
1454:10.1101/gad.1552207
1407:1998Sci...280.1599D
1350:2009FEBSL.583.1561M
1053:PAS-encoding region
856:signal transduction
732:Recent research on
624:Brandeis University
470:, functioning as a
1401:(5369): 1599–603.
1227:cyc-RA FBtr0074924
785:
747:sleep architecture
336:
1022:sleep deprivation
902:circadian rhythms
672:circadian periods
566:gender dimorphism
389:negative feedback
328:
327:
324:
323:
177:
176:
173:
172:
2260:
2232:
2231:
2213:
2181:
2175:
2174:
2164:
2154:
2130:
2124:
2123:
2105:
2081:
2075:
2074:
2041:(6886): 287–91.
2030:
2024:
2023:
2006:. 208–209: 1–6.
1999:
1993:
1992:
1990:
1988:
1977:
1971:
1970:
1934:
1928:
1927:
1917:
1907:
1883:
1877:
1876:
1866:
1834:
1828:
1827:
1817:
1785:
1779:
1778:
1760:
1736:
1730:
1729:
1719:
1679:
1673:
1672:
1662:
1630:
1624:
1623:
1590:(6886): 287–91.
1579:
1573:
1572:
1536:
1525:
1524:
1514:
1482:
1476:
1475:
1465:
1448:(13): 1687–700.
1433:
1427:
1426:
1386:
1380:
1379:
1361:
1329:
1323:
1322:
1304:
1280:
1261:
1259:
1248:
1239:
1238:
1236:
1234:
1219:
1213:
1212:
1210:
1208:
1193:
1165:Oscillating gene
1030:heat-shock genes
890:gene duplication
878:domestic chicken
872:include humans,
688:biological clock
648:forward genetics
546:heat-shock genes
452:bHLH-PAS protein
391:mechanism. The c
377:sleep-wake cycle
297:
296:
179:
178:
146:
145:
63:
39:
25:
24:
2268:
2267:
2263:
2262:
2261:
2259:
2258:
2257:
2238:
2237:
2236:
2235:
2190:Current Biology
2182:
2178:
2131:
2127:
2082:
2078:
2055:10.1038/417287a
2031:
2027:
2000:
1996:
1986:
1984:
1979:
1978:
1974:
1935:
1931:
1898:(5): e1002668.
1884:
1880:
1835:
1831:
1786:
1782:
1737:
1733:
1694:(13): 1209–15.
1688:Current Biology
1680:
1676:
1651:10.1038/nrn3208
1631:
1627:
1604:10.1038/417287a
1580:
1576:
1537:
1528:
1497:(13): 1675–86.
1483:
1479:
1434:
1430:
1387:
1383:
1330:
1326:
1281:
1264:
1250:
1249:
1242:
1232:
1230:
1221:
1220:
1216:
1206:
1204:
1195:
1194:
1190:
1185:
1176:Timeless (gene)
1141:
1114:
1077:
1042:
992:is a recessive
983:
957:
771:
678:has a dominant
620:Michael Rosbash
602:
586:homeostatically
492:phosphorylation
441:
419:are known for c
407:. The 2.17 kb c
385:gene expression
59:
46:
23:
12:
11:
5:
2266:
2256:
2255:
2250:
2234:
2233:
2176:
2145:(7): 3608–13.
2125:
2076:
2025:
1994:
1972:
1929:
1878:
1829:
1780:
1751:(5): 791–804.
1731:
1674:
1625:
1574:
1526:
1477:
1428:
1381:
1344:(10): 1561–6.
1324:
1262:
1240:
1214:
1187:
1186:
1184:
1181:
1180:
1179:
1173:
1167:
1162:
1157:
1152:
1147:
1140:
1137:
1113:
1110:
1076:
1073:
1041:
1038:
988:also known as
982:
979:
956:
953:
815:, various non-
791:gene found in
770:
767:
601:
598:
440:
437:
383:regulation of
326:
325:
322:
321:
316:
312:
311:
306:
302:
301:
293:
292:
282:
276:
275:
271:
270:
265:
259:
258:
253:
247:
246:
241:
235:
234:
229:
223:
222:
217:
211:
210:
205:
201:
200:
193:
189:
188:
184:
183:
175:
174:
171:
170:
165:
161:
160:
155:
151:
150:
142:
141:
134:
128:
127:
123:
122:
117:
111:
110:
105:
99:
98:
93:
87:
86:
81:
75:
74:
69:
65:
64:
57:
53:
52:
48:
47:
40:
32:
31:
9:
6:
4:
3:
2:
2265:
2254:
2251:
2249:
2246:
2245:
2243:
2229:
2225:
2221:
2217:
2212:
2207:
2203:
2199:
2196:(8): 638–49.
2195:
2191:
2187:
2180:
2172:
2168:
2163:
2158:
2153:
2148:
2144:
2140:
2136:
2129:
2121:
2117:
2113:
2109:
2104:
2099:
2095:
2091:
2087:
2080:
2072:
2068:
2064:
2060:
2056:
2052:
2048:
2044:
2040:
2036:
2029:
2021:
2017:
2013:
2009:
2005:
1998:
1982:
1976:
1968:
1964:
1960:
1956:
1952:
1948:
1945:(1): 149–61.
1944:
1940:
1933:
1925:
1921:
1916:
1911:
1906:
1901:
1897:
1893:
1892:PLOS Genetics
1889:
1882:
1874:
1870:
1865:
1860:
1856:
1852:
1849:(4): 706–18.
1848:
1844:
1840:
1833:
1825:
1821:
1816:
1811:
1807:
1803:
1799:
1795:
1791:
1784:
1776:
1772:
1768:
1764:
1759:
1754:
1750:
1746:
1742:
1735:
1727:
1723:
1718:
1713:
1709:
1705:
1701:
1697:
1693:
1689:
1685:
1678:
1670:
1666:
1661:
1656:
1652:
1648:
1645:(5): 325–35.
1644:
1640:
1636:
1629:
1621:
1617:
1613:
1609:
1605:
1601:
1597:
1593:
1589:
1585:
1578:
1570:
1566:
1562:
1558:
1554:
1550:
1546:
1542:
1535:
1533:
1531:
1522:
1518:
1513:
1508:
1504:
1500:
1496:
1492:
1488:
1481:
1473:
1469:
1464:
1459:
1455:
1451:
1447:
1443:
1439:
1432:
1424:
1420:
1416:
1412:
1408:
1404:
1400:
1396:
1392:
1385:
1377:
1373:
1369:
1365:
1360:
1355:
1351:
1347:
1343:
1339:
1335:
1328:
1320:
1316:
1312:
1308:
1303:
1298:
1295:(5): 805–14.
1294:
1290:
1286:
1279:
1277:
1275:
1273:
1271:
1269:
1267:
1257:
1253:
1247:
1245:
1228:
1224:
1218:
1202:
1201:cyc cyle gene
1198:
1192:
1188:
1177:
1174:
1171:
1170:Period (gene)
1168:
1166:
1163:
1161:
1158:
1156:
1153:
1151:
1148:
1146:
1145:Chronobiology
1143:
1142:
1136:
1133:
1131:
1127:
1123:
1119:
1109:
1107:
1103:
1099:
1098:
1093:
1092:transcription
1089:
1085:
1081:
1072:
1070:
1066:
1062:
1058:
1054:
1050:
1046:
1037:
1035:
1031:
1027:
1023:
1019:
1015:
1011:
1010:
1005:
1001:
1000:
995:
991:
987:
978:
976:
972:
971:
966:
962:
952:
949:
947:
942:
938:
936:
930:
926:
925:
920:
919:
914:
909:
907:
903:
899:
895:
891:
887:
883:
879:
875:
871:
867:
864:
861:
857:
853:
849:
845:
842:melanogaster
841:
837:
833:
829:
825:
822:, non insect
821:
818:
814:
810:
809:
804:
800:
796:
795:
790:
782:
781:
775:
766:
764:
760:
756:
752:
748:
744:
743:protein dimer
740:
735:
730:
727:
723:
721:
717:
713:
709:
705:
701:
697:
693:
689:
685:
681:
677:
673:
669:
665:
661:
657:
653:
650:, chemically
649:
645:
641:
637:
633:
629:
625:
621:
617:
613:
612:
607:
597:
595:
591:
587:
583:
578:
575:
571:
567:
563:
559:
555:
551:
547:
543:
539:
534:
530:
528:
524:
519:
517:
513:
509:
505:
501:
497:
493:
489:
488:casein kinase
485:
481:
477:
473:
469:
465:
461:
457:
453:
449:
445:
436:
434:
430:
426:
422:
418:
414:
410:
406:
402:
399:containing a
398:
394:
390:
386:
382:
378:
374:
370:
366:
362:
358:
357:
352:
348:
347:
342:
341:
332:
320:
317:
313:
310:
307:
303:
298:
294:
291:
290:
286:
283:
281:
277:
272:
269:
266:
264:
260:
257:
254:
252:
248:
245:
242:
240:
236:
233:
230:
228:
224:
221:
218:
216:
212:
209:
206:
202:
199:
198:
194:
190:
185:
180:
169:
166:
162:
159:
156:
152:
147:
143:
140:
139:
135:
133:
129:
124:
121:
118:
116:
112:
109:
106:
104:
103:RefSeq (Prot)
100:
97:
94:
92:
91:RefSeq (mRNA)
88:
85:
82:
80:
76:
73:
70:
66:
62:
58:
54:
49:
44:
38:
33:
30:
26:
21:
16:
2193:
2189:
2179:
2142:
2138:
2128:
2096:(2): 65–76.
2093:
2089:
2079:
2038:
2034:
2028:
2003:
1997:
1985:. Retrieved
1981:"ARNTL Gene"
1975:
1942:
1938:
1932:
1895:
1891:
1881:
1846:
1842:
1832:
1797:
1793:
1783:
1748:
1744:
1734:
1691:
1687:
1677:
1642:
1638:
1628:
1587:
1583:
1577:
1547:(1): 12–25.
1544:
1540:
1494:
1490:
1480:
1445:
1441:
1431:
1398:
1394:
1384:
1341:
1338:FEBS Letters
1337:
1327:
1292:
1288:
1255:
1231:. Retrieved
1226:
1217:
1205:. Retrieved
1200:
1191:
1134:
1125:
1117:
1115:
1105:
1095:
1079:
1078:
1068:
1064:
1060:
1044:
1043:
1033:
1025:
1017:
1007:
1003:
997:
989:
985:
984:
968:
964:
958:
944:
940:
933:
928:
922:
916:
912:
910:
862:
859:
843:
839:
835:
806:
792:
788:
786:
778:
777:A wild type
762:
758:
754:
738:
733:
731:
725:
724:
707:
703:
699:
695:
691:
683:
675:
668:heterozygote
655:
616:Jeffrey Hall
609:
605:
603:
593:
589:
581:
579:
573:
569:
561:
557:
553:
549:
541:
537:
532:
531:
520:
515:
511:
507:
503:
499:
447:
443:
442:
420:
408:
392:
372:
368:
364:
354:
345:
344:
339:
338:
337:
287:
256:NP_001025443
207:
204:Alt. symbols
195:
136:
71:
28:
15:
1800:(1): 5–14.
994:null mutant
975:mutagenized
852:PAS domains
652:mutagenzing
622:’s labs at
363:(CYC). The
309:Swiss-model
187:Identifiers
158:Swiss-model
108:NP_524168.2
96:NM_079444.3
51:Identifiers
2242:Categories
1391:Ceriani MF
1252:"Dmel/cyc"
1183:References
1090:dependent
1009:Drosophila
999:Drosophila
946:Drosophila
924:Drosophila
886:vertebrate
874:house mice
860:Drosophila
836:Drosophila
830:including
824:arthropods
813:mosquitoes
808:Drosophila
803:eukaryotes
759:Drosophila
739:Drosophila
716:PAS domain
490:-mediated
448:Drosophila
405:PAS domain
305:Structures
300:Search for
274:Other data
154:Structures
149:Search for
132:Chromosome
126:Other data
1229:. Ensembl
1104:from the
967:found in
955:Mutations
882:zebrafish
799:orthologs
797:has many
751:nutrition
680:phenotype
660:recessive
600:Discovery
425:Orthologs
381:circadian
215:NCBI gene
2228:12041977
2220:15084278
2171:10725392
2120:26099539
2112:15720403
2063:12015603
2020:28363845
1959:18850331
1939:Genetica
1924:22570630
1873:22632728
1824:22217096
1726:20541409
1669:22395806
1612:12015603
1569:28623928
1561:12568241
1521:17578907
1472:17578908
1376:22109253
1368:19376119
1319:18175560
1233:10 April
1207:10 April
1139:See also
1102:deletion
1097:timeless
1067:and the
817:dipteran
664:eclosion
468:timeless
439:Function
319:InterPro
168:InterPro
56:Organism
2198:Bibcode
2071:4401472
2043:Bibcode
1987:9 April
1967:9272820
1915:3342939
1864:3361687
1815:3265550
1775:1779880
1767:9630223
1717:2929698
1696:Bibcode
1660:3718301
1620:4401472
1592:Bibcode
1512:1899475
1463:1899476
1423:9616122
1403:Bibcode
1395:Science
1346:Bibcode
1311:9630224
1014:entrain
961:alleles
884:. Most
828:mammals
820:insects
763:cycle's
570:cyc was
417:alleles
361:protein
349:) is a
315:Domains
285:Chr. 11
263:UniProt
164:Domains
115:UniProt
2226:
2218:
2169:
2159:
2118:
2110:
2069:
2061:
2035:Nature
2018:
1965:
1957:
1922:
1912:
1871:
1861:
1843:Neuron
1822:
1812:
1773:
1765:
1724:
1714:
1667:
1657:
1618:
1610:
1584:Nature
1567:
1559:
1519:
1509:
1470:
1460:
1421:
1374:
1366:
1317:
1309:
1124:. The
1108:gene.
870:ARNTL2
832:humans
826:, and
801:among
464:period
433:ARNTL2
268:O00327
251:RefSeq
244:602550
192:Symbol
120:O61734
79:Entrez
68:Symbol
2224:S2CID
2162:16287
2116:S2CID
2067:S2CID
1963:S2CID
1771:S2CID
1616:S2CID
1565:S2CID
1372:S2CID
1315:S2CID
1178:(TIM)
1172:(PER)
1160:CLOCK
1155:ARNTL
1150:BMAL1
1088:E-box
1084:CLOCK
941:Sncyc
939:this
929:Sncyc
866:ARNTL
863:cycle
844:cycle
789:cycle
734:cycle
726:Cycle
700:clock
696:clock
692:cycle
684:Cycle
676:cycle
656:cycle
640:CLOCK
514:, or
496:video
460:E-box
456:CLOCK
444:Cycle
413:exons
367:gene
365:Cycle
340:Cycle
280:Locus
208:BMAL1
197:ARNTL
84:40162
43:Phyre
29:Cycle
2216:PMID
2167:PMID
2108:PMID
2059:PMID
2016:PMID
1989:2013
1955:PMID
1920:PMID
1869:PMID
1820:PMID
1763:PMID
1745:Cell
1722:PMID
1665:PMID
1608:PMID
1557:PMID
1517:PMID
1468:PMID
1419:PMID
1364:PMID
1307:PMID
1289:Cell
1235:2013
1209:2013
911:The
880:and
868:and
787:The
749:and
644:Cell
634:and
618:and
611:Cell
592:and
554:cyc,
550:cyc,
478:and
466:and
379:and
351:gene
239:OMIM
227:HGNC
2206:doi
2157:PMC
2147:doi
2098:doi
2051:doi
2039:417
2008:doi
1947:doi
1943:136
1910:PMC
1900:doi
1859:PMC
1851:doi
1810:PMC
1802:doi
1753:doi
1712:PMC
1704:doi
1655:PMC
1647:doi
1600:doi
1588:417
1549:doi
1507:PMC
1499:doi
1458:PMC
1450:doi
1411:doi
1399:280
1354:doi
1342:583
1297:doi
1126:cyc
1118:cyc
1112:Cyc
1106:cyc
1094:of
1080:Cyc
1075:Cyc
1069:cyc
1065:cyc
1061:cyc
1049:PER
1045:Cyc
1040:Cyc
1034:cyc
1026:cyc
1018:Cyc
1004:cyc
990:cyc
986:Cyc
981:Cyc
965:cyc
963:of
913:cyc
755:cyc
708:cyc
704:cyc
636:TIM
632:PER
614:by
606:cyc
594:cyc
590:Clk
574:cyc
562:cyc
558:cyc
542:cyc
538:cyc
533:Cyc
516:tim
512:per
508:clk
500:cyc
480:TIM
476:PER
435:).
373:yc)
353:in
346:cyc
289:p15
232:701
220:406
72:cyc
2244::
2222:.
2214:.
2204:.
2194:14
2192:.
2188:.
2165:.
2155:.
2143:97
2141:.
2137:.
2114:.
2106:.
2092:.
2088:.
2065:.
2057:.
2049:.
2037:.
2014:.
1961:.
1953:.
1941:.
1918:.
1908:.
1894:.
1890:.
1867:.
1857:.
1847:74
1845:.
1841:.
1818:.
1808:.
1798:29
1796:.
1792:.
1769:.
1761:.
1749:93
1747:.
1743:.
1720:.
1710:.
1702:.
1692:20
1690:.
1686:.
1663:.
1653:.
1643:13
1641:.
1637:.
1614:.
1606:.
1598:.
1586:.
1563:.
1555:.
1545:18
1543:.
1529:^
1515:.
1505:.
1495:21
1493:.
1489:.
1466:.
1456:.
1446:21
1444:.
1440:.
1417:.
1409:.
1397:.
1370:.
1362:.
1352:.
1340:.
1336:.
1313:.
1305:.
1293:93
1291:.
1287:.
1265:^
1254:.
1243:^
1225:.
1199:.
1116:A
908:.
876:,
854:,
840:D.
811:,
714:–
582:yc
510:,
504:yc
454:,
423:.
421:yc
409:yc
393:yc
2230:.
2208::
2200::
2173:.
2149::
2122:.
2100::
2094:4
2073:.
2053::
2045::
2022:.
2010::
1991:.
1969:.
1949::
1926:.
1902::
1896:8
1875:.
1853::
1826:.
1804::
1777:.
1755::
1728:.
1706::
1698::
1671:.
1649::
1622:.
1602::
1594::
1571:.
1551::
1523:.
1501::
1474:.
1452::
1425:.
1413::
1405::
1378:.
1356::
1348::
1321:.
1299::
1237:.
1211:.
948:,
937:,
783:.
580:C
371:c
369:(
343:(
22:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
