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O61735

- CLOCK_DROME

UniProt

O61735 - CLOCK_DROME

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
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 3 (10 May 2004)
      Previous versions | rss
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    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 binding Source: IntAct
    3. protein heterodimerization activity Source: FlyBase
    4. sequence-specific DNA binding transcription factor activity Source: InterPro
    5. signal transducer activity Source: InterPro
    6. 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

    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.

    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

    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.

    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.
    GeneTreeiENSGT00650000092935.
    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

    MDDESDDKDD TKSFLCRKSR NLSEKKRRDQ FNSLVNDLSA LISTSSRKMD     50
    KSTVLKSTIA FLKNHNEATD RSKVFEIQQD WKPAFLSNDE YTHLMLESLD 100
    GFMMVFSSMG SIFYASESIT SQLGYLPQDL YNMTIYDLAY EMDHEALLNI 150
    FMNPTPVIEP RQTDISSSNQ ITFYTHLRRG GMEKVDANAY ELVKFVGYFR 200
    NDTNTSTGSS SEVSNGSNGQ PAVLPRIFQQ NPNAEVDKKL VFVGTGRVQN 250
    PQLIREMSII DPTSNEFTSK HSMEWKFLFL DHRAPPIIGY MPFEVLGTSG 300
    YDYYHFDDLD SIVACHEELR QTGEGKSCYY RFLTKGQQWI WLQTDYYVSY 350
    HQFNSKPDYV VCTHKVVSYA EVLKDSRKEG QKSGNSNSIT NNGSSKVIAS 400
    TGTSSKSASA TTTLRDFELS SQNLDSTLLG NSLASLGTET AATSPAVDSS 450
    PMWSASAVQP SGSCQINPLK TSRPASSYGN ISSTGISPKA KRKCYFYNNR 500
    GNDSDSTSMS TDSVTSRQSM MTHVSSQSQR QRSHHREHHR ENHHNQSHHH 550
    MQQQQQHQNQ QQQHQQHQQL QQQLQHTVGT PKMVPLLPIA STQIMAGNAC 600
    QFPQPAYPLA SPQLVAPTFL EPPQYLTAIP MQPVIAPFPV APVLSPLPVQ 650
    SQTDMLPDTV VMTPTQSQLQ DQLQRKHDEL QKLILQQQNE LRIVSEQLLL 700
    SRYTYLQPMM SMGFAPGNMT AAAVGNLGAS GQRGLNFTGS NAVQPQFNQY 750
    GFALNSEQML NQQDQQMMMQ QQQNLHTQHQ HNLQQQHQSH SQLQQHTQQQ 800
    HQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQLQLQQQ NDILLREDID 850
    DIDAFLNLSP LHSLGSQSTI NPFNSSSNNN NQSYNGGSNL NNGNQNNNNR 900
    SSNPPQNNNE DSLLSCMQMA TESSPSINFH MGISDDGSET QSEDNKMMHT 950
    SGSNLVQQQQ QQQQQQQILQ QHQQQSNSFF SSNPFLNSQN QNQNQLPNDL 1000
    EILPYQMSQE QSQNLFNSPH TAPGSSQ 1027
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ENSGT00650000092935.
    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.

    Miscellaneous databases

    GenomeRNAii 38872.
    NextBioi 810786.

    Gene expression databases

    Bgeei O61735.

    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

    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: October 1, 2014
    This is version 142 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