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O61735 (CLOCK_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Circadian locomoter output cycles protein kaput
Alternative name(s):
dCLOCK
dPAS1
Gene names
Name:Clk
Synonyms:CLOCK, jrk, PAS1
ORF Names:CG7391
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length1027 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Circadian regulator that acts as a transcription factor and generates a rhythmic output with a period of about 24 hours. Oscillates in antiphase to the cycling observed for period (PER) and timeless (TIM). According to Ref.2, reaches peak abundance within several hours of the dark-light transition at ZT0 (zeitgeber 0), whereas Ref.3 describes bimodal oscillating expression with maximum at ZT5 and ZT23. Clock-cycle heterodimers activate cycling transcription of PER and TIM by binding to the E-box (5'-CACGTG-3') present in their promoters. Once induced, Period and Timeless block Clock's ability to transactivate their promoters. Ref.1

Subunit structure

Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with Cycle.

Subcellular location

Nucleus Potential.

Tissue specificity

Widely expressed. Found in head, body, and appendage fractions.

Domain

Contains three polyglutamine repeats which could correspond to the transactivation domain. The length of the repeats is polymorphic. In the arrhythmic mutant JRK, deletion of this region leads to the loss of circadian rhythmicity and altered light response.

Polymorphism

The variability in length of the polyglutamine stretch is due to polymorphism of this region. Variant B encodes two conceptual proteins, the first consists only of the bHLH domain, the other consists of the PAS-1 and all C-terminal domains. Variant B is expressed weakly at all the times of the day, and it cycles in phase with the full-length form.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
   Biological processBiological rhythms
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandDNA-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbehavioral response to cocaine

Non-traceable author statement PubMed 11715043. Source: FlyBase

circadian regulation of gene expression

Inferred from mutant phenotype PubMed 17635913. Source: FlyBase

circadian rhythm

Inferred from mutant phenotype Ref.1. Source: UniProtKB

eclosion rhythm

Non-traceable author statement PubMed 11715043. Source: FlyBase

locomotor rhythm

Inferred from mutant phenotype PubMed 12809606PubMed 12839998. Source: FlyBase

negative regulation of transcription from RNA polymerase II promoter

Non-traceable author statement PubMed 11178250. Source: FlyBase

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17578907. Source: FlyBase

positive regulation of transcription, DNA-templated

Inferred from genetic interaction Ref.3Ref.1. Source: UniProtKB

regulation of circadian sleep/wake cycle, sleep

Inferred from mutant phenotype PubMed 12015603. Source: FlyBase

rhythmic behavior

Traceable author statement PubMed 12486701. Source: FlyBase

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: InterPro

nucleus

Non-traceable author statement PubMed 12015613. Source: FlyBase

transcription factor complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionDNA binding

Non-traceable author statement Ref.3Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19376119Ref.3. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 10409723PubMed 19376119. Source: FlyBase

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

signal transducer activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from physical interaction PubMed 10409723. Source: FlyBase

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

cycO617342EBI-143834,EBI-87683

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform D (identifier: O61735-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform A (identifier: O61735-2)

The sequence of this isoform differs from the canonical sequence as follows:
     13-16: Missing.
Isoform F (identifier: O61735-3)

The sequence of this isoform differs from the canonical sequence as follows:
     2-67: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10271027Circadian locomoter output cycles protein kaput
PRO_0000127162

Regions

Domain15 – 6551bHLH
Domain88 – 16073PAS 1
Domain255 – 32167PAS 2
Region780 – 1027248Implicated in the circadian rhythmicity
Compositional bias552 – 57524Poly-Gln
Compositional bias770 – 7734Poly-Gln
Compositional bias798 – 84043Poly-Gln
Compositional bias878 – 8814Poly-Asn
Compositional bias889 – 89911Poly-Asn
Compositional bias957 – 96711Poly-Gln

Natural variations

Alternative sequence2 – 6766Missing in isoform F.
VSP_026493
Alternative sequence13 – 164Missing in isoform A.
VSP_010320
Natural variant802 – 8098Missing in variant B.

Experimental info

Sequence conflict361N → D in AAC62234. Ref.2
Sequence conflict1321N → K in AAC39101. Ref.1
Sequence conflict5591N → S in AAD10630. Ref.3
Sequence conflict6091L → I in AAC39101. Ref.1
Sequence conflict6091L → I in AAD10630. Ref.3
Sequence conflict827 – 8348Missing in AAC39101. Ref.1
Sequence conflict9161C → Y in AAC39101. Ref.1
Sequence conflict9161C → Y in AAD10630. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform D [UniParc].

Last modified May 10, 2004. Version 3.
Checksum: B4AAC80DBF6F954B

FASTA1,027116,142
        10         20         30         40         50         60 
MDDESDDKDD TKSFLCRKSR NLSEKKRRDQ FNSLVNDLSA LISTSSRKMD KSTVLKSTIA 

        70         80         90        100        110        120 
FLKNHNEATD RSKVFEIQQD WKPAFLSNDE YTHLMLESLD GFMMVFSSMG SIFYASESIT 

       130        140        150        160        170        180 
SQLGYLPQDL YNMTIYDLAY EMDHEALLNI FMNPTPVIEP RQTDISSSNQ ITFYTHLRRG 

       190        200        210        220        230        240 
GMEKVDANAY ELVKFVGYFR NDTNTSTGSS SEVSNGSNGQ PAVLPRIFQQ NPNAEVDKKL 

       250        260        270        280        290        300 
VFVGTGRVQN PQLIREMSII DPTSNEFTSK HSMEWKFLFL DHRAPPIIGY MPFEVLGTSG 

       310        320        330        340        350        360 
YDYYHFDDLD SIVACHEELR QTGEGKSCYY RFLTKGQQWI WLQTDYYVSY HQFNSKPDYV 

       370        380        390        400        410        420 
VCTHKVVSYA EVLKDSRKEG QKSGNSNSIT NNGSSKVIAS TGTSSKSASA TTTLRDFELS 

       430        440        450        460        470        480 
SQNLDSTLLG NSLASLGTET AATSPAVDSS PMWSASAVQP SGSCQINPLK TSRPASSYGN 

       490        500        510        520        530        540 
ISSTGISPKA KRKCYFYNNR GNDSDSTSMS TDSVTSRQSM MTHVSSQSQR QRSHHREHHR 

       550        560        570        580        590        600 
ENHHNQSHHH MQQQQQHQNQ QQQHQQHQQL QQQLQHTVGT PKMVPLLPIA STQIMAGNAC 

       610        620        630        640        650        660 
QFPQPAYPLA SPQLVAPTFL EPPQYLTAIP MQPVIAPFPV APVLSPLPVQ SQTDMLPDTV 

       670        680        690        700        710        720 
VMTPTQSQLQ DQLQRKHDEL QKLILQQQNE LRIVSEQLLL SRYTYLQPMM SMGFAPGNMT 

       730        740        750        760        770        780 
AAAVGNLGAS GQRGLNFTGS NAVQPQFNQY GFALNSEQML NQQDQQMMMQ QQQNLHTQHQ 

       790        800        810        820        830        840 
HNLQQQHQSH SQLQQHTQQQ HQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQLQLQQQ 

       850        860        870        880        890        900 
NDILLREDID DIDAFLNLSP LHSLGSQSTI NPFNSSSNNN NQSYNGGSNL NNGNQNNNNR 

       910        920        930        940        950        960 
SSNPPQNNNE DSLLSCMQMA TESSPSINFH MGISDDGSET QSEDNKMMHT SGSNLVQQQQ 

       970        980        990       1000       1010       1020 
QQQQQQQILQ QHQQQSNSFF SSNPFLNSQN QNQNQLPNDL EILPYQMSQE QSQNLFNSPH 


TAPGSSQ 

« Hide

Isoform A [UniParc].

Checksum: D4D271038C0D536D
Show »

FASTA1,023115,691
Isoform F [UniParc].

Checksum: 3E03838CBE0BFCD3
Show »

FASTA961108,552

References

« Hide 'large scale' references
[1]"A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless."
Allada R., White N.E., So W.V., Hall J.C., Rosbash M.
Cell 93:791-804(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION.
Tissue: Head.
[2]"Circadian regulation of a Drosophila homolog of the mammalian clock gene: PER and TIM function as positive regulators."
Bae K., Lee C., Sidote D., Chuang K.-Y., Edery I.
Mol. Cell. Biol. 18:6142-6151(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D).
Strain: Canton-S.
[3]"Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim."
Darlington T.K., Wager-Smith K., Ceriani M.F., Staknis D., Gekakis N., Steeves T.D.L., Weitz C.J., Takahashi J.S., Kay S.A.
Science 280:1599-1603(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
Tissue: Head.
[4]"The genome sequence of Drosophila melanogaster."
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. expand/collapse author list , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Berkeley.
[5]"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review."
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. expand/collapse author list , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
Strain: Berkeley.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF065133 mRNA. Translation: AAC39101.1.
AF069997 mRNA. Translation: AAC62234.1.
AF067207 mRNA. Translation: AAD10630.1.
AE014296 Genomic DNA. Translation: AAF50516.1.
AE014296 Genomic DNA. Translation: AAX52753.1.
AE014296 Genomic DNA. Translation: AAX52754.1.
PIRT13062.
T13068.
T13071.
RefSeqNP_001014574.1. NM_001014574.2. [O61735-3]
NP_001014576.1. NM_001014576.2. [O61735-1]
NP_523964.2. NM_079240.3. [O61735-2]
UniGeneDm.7596.

3D structure databases

ProteinModelPortalO61735.
SMRO61735. Positions 17-367.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid64302. 3 interactions.
DIPDIP-46595N.
IntActO61735. 2 interactions.
MINTMINT-7025605.

Proteomic databases

PaxDbO61735.
PRIDEO61735.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0100132; FBpp0099478; FBgn0023076. [O61735-1]
GeneID38872.
KEGGdme:Dmel_CG7391.
UCSCCG7391-RA. d. melanogaster. [O61735-1]

Organism-specific databases

CTD363233.
FlyBaseFBgn0023076. Clk.

Phylogenomic databases

eggNOGNOG300360.
GeneTreeENSGT00650000092935.
InParanoidO61735.
KOK02223.
OMAIVACHEE.
OrthoDBEOG71G9T7.
PhylomeDBO61735.

Gene expression databases

BgeeO61735.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
PRINTSPR00785. NCTRNSLOCATR.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi38872.
NextBio810786.

Entry information

Entry nameCLOCK_DROME
AccessionPrimary (citable) accession number: O61735
Secondary accession number(s): A4V1L9 expand/collapse secondary AC list , A4V1M0, O76342, O77137, Q59E25, Q9VSB0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 10, 2004
Last modified: July 9, 2014
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase