CYCL_DROME
ID CYCL_DROME Reviewed; 413 AA.
AC O61734; O76344; Q1LZ29; Q540W7; Q9VW44;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Protein cycle;
DE AltName: Full=Brain and muscle ARNT-like 1;
DE Short=BMAL1;
DE AltName: Full=MOP3;
GN Name=cyc; ORFNames=CG8727;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DISRUPTION PHENOTYPE.
RC TISSUE=Ovary;
RX PubMed=9630224; DOI=10.1016/s0092-8674(00)81441-5;
RA Rutila J.E., Suri V., Le M., So W.V., Rosbash M., Hall J.C.;
RT "CYCLE is a second bHLH-PAS clock protein essential for circadian
RT rhythmicity and transcription of Drosophila period and timeless.";
RL Cell 93:805-814(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain, and Muscle;
RX PubMed=9616122; DOI=10.1126/science.280.5369.1599;
RA Darlington T.K., Wager-Smith K., Ceriani M.F., Staknis D., Gekakis N.,
RA Steeves T.D.L., Weitz C.J., Takahashi J.S., Kay S.A.;
RT "Closing the circadian loop: CLOCK-induced transcription of its own
RT inhibitors per and tim.";
RL Science 280:1599-1603(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bae K.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Putative transcription factor involved in the generation of
CC biological rhythms. Activates cycling transcription of Period (PER) and
CC Timeless (TIM) by binding to the E-box (5'-CACGTG-3') present in their
CC promoters.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms a heterodimer with Clock in order to activate PER and
CC TIM transcription.
CC -!- INTERACTION:
CC O61734; O61735: Clk; NbExp=3; IntAct=EBI-87683, EBI-143834;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Expressed in head and ovary.
CC -!- DISRUPTION PHENOTYPE: Cyc mutants don't display PER and TIM cycling,
CC and are completely arrhythmic. {ECO:0000269|PubMed:9630224}.
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DR EMBL; AF065473; AAC39124.1; -; mRNA.
DR EMBL; AF067206; AAD10629.1; -; mRNA.
DR EMBL; AF069998; AAC62235.1; -; mRNA.
DR EMBL; AE014296; AAF49107.1; -; Genomic_DNA.
DR EMBL; AY119284; AAM51144.1; -; mRNA.
DR EMBL; BT025197; ABF17888.1; -; mRNA.
DR RefSeq; NP_524168.2; NM_079444.3.
DR PDB; 5F5Y; X-ray; 2.20 A; A=311-412.
DR PDB; 5F68; X-ray; 1.23 A; A=311-412.
DR PDB; 5F69; X-ray; 1.37 A; A=311-412.
DR PDB; 5F6A; X-ray; 1.93 A; A=311-412.
DR PDBsum; 5F5Y; -.
DR PDBsum; 5F68; -.
DR PDBsum; 5F69; -.
DR PDBsum; 5F6A; -.
DR AlphaFoldDB; O61734; -.
DR SMR; O61734; -.
DR BioGRID; 65431; 10.
DR IntAct; O61734; 7.
DR MINT; O61734; -.
DR STRING; 7227.FBpp0074693; -.
DR PaxDb; O61734; -.
DR PRIDE; O61734; -.
DR DNASU; 40162; -.
DR EnsemblMetazoa; FBtr0074924; FBpp0074693; FBgn0023094.
DR GeneID; 40162; -.
DR KEGG; dme:Dmel_CG8727; -.
DR CTD; 40162; -.
DR FlyBase; FBgn0023094; cyc.
DR VEuPathDB; VectorBase:FBgn0023094; -.
DR eggNOG; KOG3561; Eukaryota.
DR HOGENOM; CLU_011864_0_0_1; -.
DR InParanoid; O61734; -.
DR OMA; MEVQEFC; -.
DR OrthoDB; 331262at2759; -.
DR PhylomeDB; O61734; -.
DR Reactome; R-DME-432395; Degradation of TIM.
DR Reactome; R-DME-432408; Transcription regulation of cwo gene.
DR Reactome; R-DME-432501; Transcription repression by PER and activation by PDP1.
DR Reactome; R-DME-432524; Degradation of PER.
DR Reactome; R-DME-432560; Transcription activation by CLK:CYC and repression by VRI.
DR Reactome; R-DME-432620; Dephosphorylation of PER.
DR Reactome; R-DME-432626; Circadian Clock pathway.
DR BioGRID-ORCS; 40162; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40162; -.
DR PRO; PR:O61734; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0023094; Expressed in adult abdomen and 28 other tissues.
DR Genevisible; O61734; DM.
DR GO; GO:0034751; C:aryl hydrocarbon receptor complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:FlyBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0048148; P:behavioral response to cocaine; TAS:FlyBase.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:FlyBase.
DR GO; GO:0003053; P:circadian regulation of heart rate; IMP:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; TAS:FlyBase.
DR GO; GO:0008062; P:eclosion rhythm; TAS:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; TAS:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; TAS:FlyBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; TAS:FlyBase.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IMP:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0042594; P:response to starvation; IDA:FlyBase.
DR GO; GO:0007622; P:rhythmic behavior; TAS:FlyBase.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Biological rhythms; DNA-binding; Nucleus; Reference proteome;
KW Repeat; Transcription; Transcription regulation.
FT CHAIN 1..413
FT /note="Protein cycle"
FT /id="PRO_0000127165"
FT DOMAIN 30..83
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 104..175
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 297..367
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 372..413
FT /note="PAC"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..237
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 35
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 38
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 39
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT SITE 43
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O00327"
FT CONFLICT 242
FT /note="T -> S (in Ref. 1; AAC39124, 2; AAD10629, 3;
FT AAC62235 and 6; AAM51144)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="H -> Y (in Ref. 1; AAC39124)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="M -> V (in Ref. 1; AAC39124)"
FT /evidence="ECO:0000305"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:5F68"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:5F68"
FT HELIX 328..332
FT /evidence="ECO:0007829|PDB:5F68"
FT HELIX 336..339
FT /evidence="ECO:0007829|PDB:5F68"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:5F68"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:5F68"
FT HELIX 353..365
FT /evidence="ECO:0007829|PDB:5F68"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:5F69"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:5F68"
FT STRAND 384..395
FT /evidence="ECO:0007829|PDB:5F68"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:5F68"
FT STRAND 402..411
FT /evidence="ECO:0007829|PDB:5F68"
SQ SEQUENCE 413 AA; 47569 MW; 061C1769E6BBDB0D CRC64;
MEVQEFCENM EEIEDENYDE EKSARTSDEN RKQNHSEIEK RRRDKMNTYI NELSSMIPMC
FAMQRKLDKL TVLRMAVQHL RGIRGSGSLH PFNGSDYRPS FLSDQELKMI ILQASEGFLF
VVGCDRGRIL YVSDSVSSVL NSTQADLLGQ SWFDVLHPKD IGKVKEQLSS LEQCPRERLI
DAKTMLPVKT DVPQSLCRLC PGARRSFFCR MKLRTASNNQ IKEESDTSSS SRSSTKRKSR
LTTGHKYRVI QCTGYLKSWT PIKDEDQDAD SDEQTTNLSC LVAIGRIPPN VRNSTVPASL
DNHPNIRHVL FISRHSGEGK FLFIDQRATL VIGFLPQEIL GTSFYEYFHN EDIAALMESH
KMVMQVPEKV TTQVYRFRCK DNSYIQLQSE WRAFKNPWTS EIDYIIAKNS VFL
