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O61735

- CLOCK_DROME

UniProt

O61735 - CLOCK_DROME

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Protein

Circadian locomoter output cycles protein kaput

Gene

Clk

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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 PubMed:9742131, reaches peak abundance within several hours of the dark-light transition at ZT0 (zeitgeber 0), whereas PubMed:9616122 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.1 Publication

GO - Molecular functioni

  1. DNA binding Source: UniProtKB
  2. protein heterodimerization activity Source: FlyBase
  3. sequence-specific DNA binding transcription factor activity Source: InterPro
  4. signal transducer activity Source: InterPro
  5. transcription factor binding Source: FlyBase

GO - Biological processi

  1. behavioral response to cocaine Source: FlyBase
  2. circadian regulation of gene expression Source: FlyBase
  3. circadian rhythm Source: UniProtKB
  4. eclosion rhythm Source: FlyBase
  5. locomotor rhythm Source: FlyBase
  6. negative regulation of transcription from RNA polymerase II promoter Source: FlyBase
  7. positive regulation of transcription, DNA-templated Source: UniProtKB
  8. positive regulation of transcription from RNA polymerase II promoter Source: FlyBase
  9. regulation of circadian sleep/wake cycle, sleep Source: FlyBase
  10. rhythmic behavior Source: FlyBase
  11. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_180268. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
REACT_180846. PPARA activates gene expression.
REACT_181316. RORA activates circadian gene expression.
REACT_181317. REV-ERBA represses gene expression.
REACT_239233. Circadian Clock.

Names & Taxonomyi

Protein namesi
Recommended name:
Circadian locomoter output cycles protein kaput
Alternative name(s):
dCLOCK
dPAS1
Gene namesi
Name:Clk
Synonyms:CLOCK, jrk, PAS1
ORF Names:CG7391
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
ProteomesiUP000000803: Chromosome 3L

Organism-specific databases

FlyBaseiFBgn0023076. Clk.

Subcellular locationi

Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. cytoplasm Source: InterPro
  2. nucleus Source: FlyBase
  3. transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10271027Circadian locomoter output cycles protein kaputPRO_0000127162Add
BLAST

Proteomic databases

PaxDbiO61735.
PRIDEiO61735.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO61735.
ExpressionAtlasiO61735. differential.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
cycO617342EBI-143834,EBI-87683

Protein-protein interaction databases

BioGridi64302. 3 interactions.
DIPiDIP-46595N.
IntActiO61735. 2 interactions.
MINTiMINT-7025605.

Structurei

3D structure databases

ProteinModelPortaliO61735.
SMRiO61735. Positions 17-367.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini15 – 6551bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini88 – 16073PAS 1PROSITE-ProRule annotationAdd
BLAST
Domaini255 – 32167PAS 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni780 – 1027248Implicated in the circadian rhythmicityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi552 – 57524Poly-GlnAdd
BLAST
Compositional biasi770 – 7734Poly-Gln
Compositional biasi798 – 84043Poly-GlnAdd
BLAST
Compositional biasi878 – 8814Poly-Asn
Compositional biasi889 – 89911Poly-AsnAdd
BLAST
Compositional biasi957 – 96711Poly-GlnAdd
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG300360.
GeneTreeiENSGT00760000118788.
InParanoidiO61735.
KOiK02223.
OMAiIVACHEE.
OrthoDBiEOG71G9T7.
PhylomeDBiO61735.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
PRINTSiPR00785. NCTRNSLOCATR.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform D (identifier: O61735-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MDDESDDKDD TKSFLCRKSR NLSEKKRRDQ FNSLVNDLSA LISTSSRKMD
60 70 80 90 100
KSTVLKSTIA FLKNHNEATD RSKVFEIQQD WKPAFLSNDE YTHLMLESLD
110 120 130 140 150
GFMMVFSSMG SIFYASESIT SQLGYLPQDL YNMTIYDLAY EMDHEALLNI
160 170 180 190 200
FMNPTPVIEP RQTDISSSNQ ITFYTHLRRG GMEKVDANAY ELVKFVGYFR
210 220 230 240 250
NDTNTSTGSS SEVSNGSNGQ PAVLPRIFQQ NPNAEVDKKL VFVGTGRVQN
260 270 280 290 300
PQLIREMSII DPTSNEFTSK HSMEWKFLFL DHRAPPIIGY MPFEVLGTSG
310 320 330 340 350
YDYYHFDDLD SIVACHEELR QTGEGKSCYY RFLTKGQQWI WLQTDYYVSY
360 370 380 390 400
HQFNSKPDYV VCTHKVVSYA EVLKDSRKEG QKSGNSNSIT NNGSSKVIAS
410 420 430 440 450
TGTSSKSASA TTTLRDFELS SQNLDSTLLG NSLASLGTET AATSPAVDSS
460 470 480 490 500
PMWSASAVQP SGSCQINPLK TSRPASSYGN ISSTGISPKA KRKCYFYNNR
510 520 530 540 550
GNDSDSTSMS TDSVTSRQSM MTHVSSQSQR QRSHHREHHR ENHHNQSHHH
560 570 580 590 600
MQQQQQHQNQ QQQHQQHQQL QQQLQHTVGT PKMVPLLPIA STQIMAGNAC
610 620 630 640 650
QFPQPAYPLA SPQLVAPTFL EPPQYLTAIP MQPVIAPFPV APVLSPLPVQ
660 670 680 690 700
SQTDMLPDTV VMTPTQSQLQ DQLQRKHDEL QKLILQQQNE LRIVSEQLLL
710 720 730 740 750
SRYTYLQPMM SMGFAPGNMT AAAVGNLGAS GQRGLNFTGS NAVQPQFNQY
760 770 780 790 800
GFALNSEQML NQQDQQMMMQ QQQNLHTQHQ HNLQQQHQSH SQLQQHTQQQ
810 820 830 840 850
HQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQLQLQQQ NDILLREDID
860 870 880 890 900
DIDAFLNLSP LHSLGSQSTI NPFNSSSNNN NQSYNGGSNL NNGNQNNNNR
910 920 930 940 950
SSNPPQNNNE DSLLSCMQMA TESSPSINFH MGISDDGSET QSEDNKMMHT
960 970 980 990 1000
SGSNLVQQQQ QQQQQQQILQ QHQQQSNSFF SSNPFLNSQN QNQNQLPNDL
1010 1020
EILPYQMSQE QSQNLFNSPH TAPGSSQ
Length:1,027
Mass (Da):116,142
Last modified:May 10, 2004 - v3
Checksum:iB4AAC80DBF6F954B
GO
Isoform A (identifier: O61735-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     13-16: Missing.

Show »
Length:1,023
Mass (Da):115,691
Checksum:iD4D271038C0D536D
GO
Isoform F (identifier: O61735-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-67: Missing.

Note: No experimental confirmation available.

Show »
Length:961
Mass (Da):108,552
Checksum:i3E03838CBE0BFCD3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti36 – 361N → D in AAC62234. (PubMed:9742131)Curated
Sequence conflicti132 – 1321N → K in AAC39101. (PubMed:9630223)Curated
Sequence conflicti559 – 5591N → S in AAD10630. (PubMed:9616122)Curated
Sequence conflicti609 – 6091L → I in AAC39101. (PubMed:9630223)Curated
Sequence conflicti609 – 6091L → I in AAD10630. (PubMed:9616122)Curated
Sequence conflicti827 – 8348Missing in AAC39101. (PubMed:9630223)Curated
Sequence conflicti916 – 9161C → Y in AAC39101. (PubMed:9630223)Curated
Sequence conflicti916 – 9161C → Y in AAD10630. (PubMed:9616122)Curated

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti802 – 8098Missing in variant B.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 6766Missing in isoform F. CuratedVSP_026493Add
BLAST
Alternative sequencei13 – 164Missing in isoform A. 2 PublicationsVSP_010320

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiT13062.
T13068.
T13071.
RefSeqiNP_001014574.1. NM_001014574.2. [O61735-3]
NP_001014576.1. NM_001014576.2. [O61735-1]
NP_523964.2. NM_079240.3. [O61735-2]
UniGeneiDm.7596.

Genome annotation databases

EnsemblMetazoaiFBtr0100132; FBpp0099478; FBgn0023076. [O61735-1]
GeneIDi38872.
KEGGidme:Dmel_CG7391.
UCSCiCG7391-RA. d. melanogaster. [O61735-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
PIRi T13062.
T13068.
T13071.
RefSeqi NP_001014574.1. NM_001014574.2. [O61735-3 ]
NP_001014576.1. NM_001014576.2. [O61735-1 ]
NP_523964.2. NM_079240.3. [O61735-2 ]
UniGenei Dm.7596.

3D structure databases

ProteinModelPortali O61735.
SMRi O61735. Positions 17-367.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 64302. 3 interactions.
DIPi DIP-46595N.
IntActi O61735. 2 interactions.
MINTi MINT-7025605.

Proteomic databases

PaxDbi O61735.
PRIDEi O61735.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblMetazoai FBtr0100132 ; FBpp0099478 ; FBgn0023076 . [O61735-1 ]
GeneIDi 38872.
KEGGi dme:Dmel_CG7391.
UCSCi CG7391-RA. d. melanogaster. [O61735-1 ]

Organism-specific databases

CTDi 363233.
FlyBasei FBgn0023076. Clk.

Phylogenomic databases

eggNOGi NOG300360.
GeneTreei ENSGT00760000118788.
InParanoidi O61735.
KOi K02223.
OMAi IVACHEE.
OrthoDBi EOG71G9T7.
PhylomeDBi O61735.

Enzyme and pathway databases

Reactomei REACT_180268. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
REACT_180846. PPARA activates gene expression.
REACT_181316. RORA activates circadian gene expression.
REACT_181317. REV-ERBA represses gene expression.
REACT_239233. Circadian Clock.

Miscellaneous databases

GenomeRNAii 38872.
NextBioi 810786.

Gene expression databases

Bgeei O61735.
ExpressionAtlasi O61735. differential.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
[Graphical view ]
Pfami PF00010. HLH. 1 hit.
[Graphical view ]
PRINTSi PR00785. NCTRNSLOCATR.
SMARTi SM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEi PS50888. BHLH. 1 hit.
PS50112. PAS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
    Strain: Berkeley.

Entry informationi

Entry nameiCLOCK_DROME
AccessioniPrimary (citable) accession number: O61735
Secondary accession number(s): A4V1L9
, A4V1M0, O76342, O77137, Q59E25, Q9VSB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 10, 2004
Last modified: November 26, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3