CLOCK_DROME
ID CLOCK_DROME Reviewed; 1027 AA.
AC O61735; A4V1L9; A4V1M0; O76342; O77137; Q59E25; Q9VSB0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Circadian locomoter output cycles protein kaput;
DE AltName: Full=dCLOCK;
DE AltName: Full=dPAS1;
GN Name=Clk; Synonyms=CLOCK, jrk, PAS1; ORFNames=CG7391;
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] (ISOFORM A), AND FUNCTION.
RC TISSUE=Head;
RX PubMed=9630223; DOI=10.1016/s0092-8674(00)81440-3;
RA Allada R., White N.E., So W.V., Hall J.C., Rosbash M.;
RT "A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms
RT and transcription of period and timeless.";
RL Cell 93:791-804(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D).
RC STRAIN=Canton-S;
RX PubMed=9742131; DOI=10.1128/mcb.18.10.6142;
RA Bae K., Lee C., Sidote D., Chuang K.-Y., Edery I.;
RT "Circadian regulation of a Drosophila homolog of the mammalian clock gene:
RT PER and TIM function as positive regulators.";
RL Mol. Cell. Biol. 18:6142-6151(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Head;
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 [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, AND ALTERNATIVE SPLICING.
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).
CC -!- FUNCTION: Circadian regulator that acts as a transcription factor and
CC generates a rhythmic output with a period of about 24 hours. Oscillates
CC in antiphase to the cycling observed for period (PER) and timeless
CC (TIM). According to PubMed:9742131, reaches peak abundance within
CC several hours of the dark-light transition at ZT0 (zeitgeber 0),
CC whereas PubMed:9616122 describes bimodal oscillating expression with
CC maximum at ZT5 and ZT23. Clock-cycle heterodimers activate cycling
CC transcription of PER and TIM by binding to the E-box (5'-CACGTG-3')
CC present in their promoters. Once induced, Period and Timeless block
CC Clock's ability to transactivate their promoters.
CC {ECO:0000269|PubMed:9630223}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms a heterodimer with Cycle.
CC -!- INTERACTION:
CC O61735; P08181: CkIIalpha; NbExp=2; IntAct=EBI-143834, EBI-93115;
CC O61735; O61734: cyc; NbExp=3; IntAct=EBI-143834, EBI-87683;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=D;
CC IsoId=O61735-1; Sequence=Displayed;
CC Name=A;
CC IsoId=O61735-2; Sequence=VSP_010320;
CC Name=F;
CC IsoId=O61735-3; Sequence=VSP_026493;
CC -!- TISSUE SPECIFICITY: Widely expressed. Found in head, body, and
CC appendage fractions.
CC -!- DOMAIN: Contains three polyglutamine repeats which could correspond to
CC the transactivation domain. The length of the repeats is polymorphic.
CC In the arrhythmic mutant JRK, deletion of this region leads to the loss
CC of circadian rhythmicity and altered light response.
CC -!- POLYMORPHISM: The variability in length of the polyglutamine stretch is
CC due to polymorphism of this region. Variant B encodes two conceptual
CC proteins, the first consists only of the bHLH domain, the other
CC consists of the PAS-1 and all C-terminal domains. Variant B is
CC expressed weakly at all the times of the day, and it cycles in phase
CC with the full-length form.
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DR EMBL; AF065133; AAC39101.1; -; mRNA.
DR EMBL; AF069997; AAC62234.1; -; mRNA.
DR EMBL; AF067207; AAD10630.1; -; mRNA.
DR EMBL; AE014296; AAF50516.1; -; Genomic_DNA.
DR EMBL; AE014296; AAX52753.1; -; Genomic_DNA.
DR EMBL; AE014296; AAX52754.1; -; Genomic_DNA.
DR PIR; T13062; T13062.
DR PIR; T13068; T13068.
DR PIR; T13071; T13071.
DR RefSeq; NP_001014574.1; NM_001014574.2. [O61735-3]
DR RefSeq; NP_001014576.1; NM_001014576.2. [O61735-1]
DR RefSeq; NP_523964.2; NM_079240.3. [O61735-2]
DR AlphaFoldDB; O61735; -.
DR SMR; O61735; -.
DR BioGRID; 64302; 27.
DR DIP; DIP-46595N; -.
DR IntAct; O61735; 18.
DR MINT; O61735; -.
DR STRING; 7227.FBpp0099478; -.
DR iPTMnet; O61735; -.
DR PaxDb; O61735; -.
DR PRIDE; O61735; -.
DR EnsemblMetazoa; FBtr0076785; FBpp0076500; FBgn0023076. [O61735-2]
DR EnsemblMetazoa; FBtr0100132; FBpp0099478; FBgn0023076. [O61735-1]
DR EnsemblMetazoa; FBtr0100134; FBpp0099480; FBgn0023076. [O61735-3]
DR GeneID; 38872; -.
DR KEGG; dme:Dmel_CG7391; -.
DR UCSC; CG7391-RA; d. melanogaster. [O61735-1]
DR CTD; 38872; -.
DR FlyBase; FBgn0023076; Clk.
DR VEuPathDB; VectorBase:FBgn0023076; -.
DR eggNOG; KOG3561; Eukaryota.
DR GeneTree; ENSGT00940000169943; -.
DR InParanoid; O61735; -.
DR OMA; SPMWSAT; -.
DR PhylomeDB; O61735; -.
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 SignaLink; O61735; -.
DR BioGRID-ORCS; 38872; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38872; -.
DR PRO; PR:O61735; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0023076; Expressed in spermathecum and 17 other tissues.
DR ExpressionAtlas; O61735; baseline and differential.
DR Genevisible; O61735; DM.
DR GO; GO:1990513; C:CLOCK-BMAL transcription complex; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; NAS:FlyBase.
DR GO; GO:0003682; F:chromatin binding; IDA:FlyBase.
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:0008134; F:transcription factor binding; IPI:FlyBase.
DR GO; GO:0048148; P:behavioral response to cocaine; TAS:FlyBase.
DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:FlyBase.
DR GO; GO:0003053; P:circadian regulation of heart rate; IMP:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; IMP:UniProtKB.
DR GO; GO:0008062; P:eclosion rhythm; TAS:FlyBase.
DR GO; GO:0009649; P:entrainment of circadian clock; IMP:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; IMP:FlyBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; NAS:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IGI:UniProtKB.
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:0009416; P:response to light stimulus; IDA:FlyBase.
DR GO; GO:0009266; P:response to temperature stimulus; 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; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR Pfam; PF00010; HLH; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 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; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Biological rhythms; DNA-binding; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..1027
FT /note="Circadian locomoter output cycles protein kaput"
FT /id="PRO_0000127162"
FT DOMAIN 15..65
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 88..160
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 255..321
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT REGION 377..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 765..800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..1027
FT /note="Implicated in the circadian rhythmicity"
FT REGION 869..911
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 926..1027
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 443..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 499..528
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 532..546
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..575
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 944..1027
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 20
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT SITE 24
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT SITE 28
FT /note="Interaction with E-box DNA"
FT /evidence="ECO:0000250|UniProtKB:O15516"
FT VAR_SEQ 2..67
FT /note="Missing (in isoform F)"
FT /evidence="ECO:0000305"
FT /id="VSP_026493"
FT VAR_SEQ 13..16
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:9616122,
FT ECO:0000303|PubMed:9630223"
FT /id="VSP_010320"
FT VARIANT 802..809
FT /note="Missing (in variant B)"
FT CONFLICT 36
FT /note="N -> D (in Ref. 2; AAC62234)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="N -> K (in Ref. 1; AAC39101)"
FT /evidence="ECO:0000305"
FT CONFLICT 559
FT /note="N -> S (in Ref. 3; AAD10630)"
FT /evidence="ECO:0000305"
FT CONFLICT 609
FT /note="L -> I (in Ref. 1; AAC39101 and 3; AAD10630)"
FT /evidence="ECO:0000305"
FT CONFLICT 827..834
FT /note="Missing (in Ref. 1; AAC39101)"
FT /evidence="ECO:0000305"
FT CONFLICT 916
FT /note="C -> Y (in Ref. 1; AAC39101 and 3; AAD10630)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1027 AA; 116142 MW; B4AAC80DBF6F954B CRC64;
MDDESDDKDD TKSFLCRKSR NLSEKKRRDQ FNSLVNDLSA LISTSSRKMD KSTVLKSTIA
FLKNHNEATD RSKVFEIQQD WKPAFLSNDE YTHLMLESLD GFMMVFSSMG SIFYASESIT
SQLGYLPQDL YNMTIYDLAY EMDHEALLNI FMNPTPVIEP RQTDISSSNQ ITFYTHLRRG
GMEKVDANAY ELVKFVGYFR NDTNTSTGSS SEVSNGSNGQ PAVLPRIFQQ NPNAEVDKKL
VFVGTGRVQN PQLIREMSII DPTSNEFTSK HSMEWKFLFL DHRAPPIIGY MPFEVLGTSG
YDYYHFDDLD SIVACHEELR QTGEGKSCYY RFLTKGQQWI WLQTDYYVSY HQFNSKPDYV
VCTHKVVSYA EVLKDSRKEG QKSGNSNSIT NNGSSKVIAS TGTSSKSASA TTTLRDFELS
SQNLDSTLLG NSLASLGTET AATSPAVDSS PMWSASAVQP SGSCQINPLK TSRPASSYGN
ISSTGISPKA KRKCYFYNNR GNDSDSTSMS TDSVTSRQSM MTHVSSQSQR QRSHHREHHR
ENHHNQSHHH MQQQQQHQNQ QQQHQQHQQL QQQLQHTVGT PKMVPLLPIA STQIMAGNAC
QFPQPAYPLA SPQLVAPTFL EPPQYLTAIP MQPVIAPFPV APVLSPLPVQ SQTDMLPDTV
VMTPTQSQLQ DQLQRKHDEL QKLILQQQNE LRIVSEQLLL SRYTYLQPMM SMGFAPGNMT
AAAVGNLGAS GQRGLNFTGS NAVQPQFNQY GFALNSEQML NQQDQQMMMQ QQQNLHTQHQ
HNLQQQHQSH SQLQQHTQQQ HQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQLQLQQQ
NDILLREDID DIDAFLNLSP LHSLGSQSTI NPFNSSSNNN NQSYNGGSNL NNGNQNNNNR
SSNPPQNNNE DSLLSCMQMA TESSPSINFH MGISDDGSET QSEDNKMMHT SGSNLVQQQQ
QQQQQQQILQ QHQQQSNSFF SSNPFLNSQN QNQNQLPNDL EILPYQMSQE QSQNLFNSPH
TAPGSSQ
