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P49021 (TIM_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein timeless
Gene names
Name:tim
ORF Names:CG3234
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length1421 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for the production of circadian rhythms. The biological cycle depends on the rhythmic formation and nuclear localization of the TIM-PER complex. Light induces the degradation of TIM, which promotes elimination of PER. Nuclear activity of the heterodimer coordinatively regulates PER and TIM transcription through a negative feedback loop. Behaves as a negative element in circadian transcriptional loop. Does not appear to bind DNA, suggesting indirect transcriptional inhibition.

Subunit structure

Forms a heterodimer with period (PER); the complex then translocates into the nucleus.

Subcellular location

Nucleus. Cytoplasmperinuclear region. Note: Nuclear at specific periods of the day. First accumulates in the perinuclear region about one hour before translocation into the nucleus. Interaction with per is required for nuclear localization.

Tissue specificity

Isoform D is expressed in the head.

Post-translational modification

Phosphorylated with a circadian rhythmicity.

Polymorphism

A polymorphism identified in some strains generates a premature stop codon shortly after Met-1; in this case Met-24 is the start site.

Sequence similarities

Belongs to the timeless family.

Sequence caution

The sequence AAL13507.1 differs from that shown. Reason: Intron retention.

The sequence AAN71179.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processBiological rhythms
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative initiation
Alternative splicing
Polymorphism
   DomainRepeat
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to light stimulus

Inferred from mutant phenotype PubMed 9697866. Source: FlyBase

circadian behavior

Inferred from mutant phenotype PubMed 11333398. Source: FlyBase

circadian rhythm

Non-traceable author statement PubMed 11715043. Source: FlyBase

circadian temperature homeostasis

Inferred from mutant phenotype PubMed 22981774. Source: FlyBase

copulation

Inferred from mutant phenotype PubMed 15324667. Source: FlyBase

eclosion rhythm

Non-traceable author statement PubMed 11715043. Source: FlyBase

entrainment of circadian clock

Traceable author statement PubMed 11178250. Source: FlyBase

locomotor rhythm

Inferred from genetic interaction PubMed 17068124. Source: FlyBase

mating behavior

Inferred from mutant phenotype PubMed 11470898. Source: FlyBase

negative phototaxis

Inferred from mutant phenotype PubMed 19285485. Source: FlyBase

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10409723. Source: FlyBase

negative regulation of transcription regulatory region DNA binding

Inferred from direct assay PubMed 10409723. Source: FlyBase

photoperiodism

Inferred from mutant phenotype PubMed 17600215. Source: FlyBase

protein import into nucleus

Non-traceable author statement PubMed 12015613. Source: FlyBase

regulation of circadian sleep/wake cycle

Inferred from mutant phenotype PubMed 16938867. Source: FlyBase

regulation of circadian sleep/wake cycle, sleep

Inferred from mutant phenotype PubMed 12015603. Source: FlyBase

regulation of protein import into nucleus

Traceable author statement PubMed 11178250. Source: FlyBase

rhythmic behavior

Traceable author statement PubMed 12486701. Source: FlyBase

sleep

Non-traceable author statement PubMed 11715043. Source: FlyBase

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10417378PubMed 12944510PubMed 16410523PubMed 17369364. Source: FlyBase

nucleus

Inferred from direct assay PubMed 12944510PubMed 16410523PubMed 17369364. Source: FlyBase

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

protein complex

Inferred from physical interaction PubMed 10417378. Source: FlyBase

   Molecular_functionprotein heterodimerization activity

Inferred from physical interaction PubMed 10409723. Source: FlyBase

transcription factor binding

Inferred from physical interaction PubMed 10409723. Source: FlyBase

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform D (identifier: P49021-1)

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: P49021-2)

The sequence of this isoform differs from the canonical sequence as follows:
     260-291: Missing.
Note: Apparently not implicated in circadian rhythms causing a long-period phenotype and arrhythmia.
Isoform C (identifier: P49021-3)

The sequence of this isoform differs from the canonical sequence as follows:
     914-914: C → W
     915-1421: Missing.
Note: No experimental confirmation available.
Isoform B (identifier: P49021-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.
Note: Produced by alternative initiation at Met-24 of isoform D.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14211421Protein timeless
PRO_0000022532

Regions

Region260 – 29132Necessary for normal circadian rhythm
Motif573 – 58311Nuclear localization signal Potential
Compositional bias184 – 1874Poly-Leu
Compositional bias383 – 41230Asp/Glu-rich (acidic)
Compositional bias405 – 4128Poly-Glu
Compositional bias455 – 4606Poly-Pro
Compositional bias1309 – 13124Poly-Ser
Compositional bias1333 – 13364Poly-Gly

Natural variations

Alternative sequence1 – 2323Missing in isoform B.
VSP_018822
Alternative sequence260 – 29132Missing in isoform A.
VSP_004457
Alternative sequence9141C → W in isoform C.
VSP_007693
Alternative sequence915 – 1421507Missing in isoform C.
VSP_007694

Experimental info

Sequence conflict12561V → I in AAF51097. Ref.3
Sequence conflict12561V → I in AAF51098. Ref.3
Sequence conflict12561V → I in AAN10371. Ref.3
Sequence conflict12561V → I in AAN71179. Ref.3

Sequences

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

Last modified July 15, 1999. Version 2.
Checksum: 12C24FF4E0833966

FASTA1,421159,201
        10         20         30         40         50         60 
MSRVRQLHNH IWNNQNFDKV KSVMDWLLAT PQLYSAFSSL GCLEGDTYVV NPNALAILEE 

        70         80         90        100        110        120 
INYKLTYEDQ TLRTFRRAIG FGQNVRSDLI PLLENAKDDA VLESVIRILV NLTVPVECLF 

       130        140        150        160        170        180 
SVDVMYRTDV GRHTIFELNK LLYTSKEAFT EARSTKSVVE YMKHILESDP KLSPHKCDQI 

       190        200        210        220        230        240 
NNCLLLLRNI LHIPETHAHC VMPMMQSMPH GISMQNTILW NLFIQSIDKL LLYLMTCPQR 

       250        260        270        280        290        300 
AFWGVTMVQL IALIYKDQHV STLQKLLSLW FEASLSESSE DNESNTSPPK QGSGDSSPML 

       310        320        330        340        350        360 
TSDPTSDSSD NGSNGRGMGG GMREGTAATL QEVSRKGQEY QNAMARVPAD KPDGSEEASD 

       370        380        390        400        410        420 
MTGNDSEQPG SPEQSQPAGE SMDDGDYEDQ RHRQLNEHGE EDEDEDEVEE EEYLQLGPAS 

       430        440        450        460        470        480 
EPLNLTQQPA DKVNNTTNPT SSAPQGCLGN EPFKPPPPLP VRASTSAHAQ MQKFNESSYA 

       490        500        510        520        530        540 
SHVSAVKLGQ KSPHAGQLQL TKGKCCPQKR ECPSSQSELS DCGYGTQVEN QESISTSSND 

       550        560        570        580        590        600 
DDGPQGKPQH QKPPCNTKPR NKPRTIMSPM DKKELRRKKL VKRSKSSLIN MKGLVQHTPT 

       610        620        630        640        650        660 
DDDISNLLKE FTVDFLLKGY SYLVEELHMQ LLSNAKVPID TSHFFWLVTY FLKFAAQLEL 

       670        680        690        700        710        720 
DMEHIDTILT YDVLSYLTYE GVSLCEQLEL NARQEGSDLK PYLRRMHLVV TAIREFLQAI 

       730        740        750        760        770        780 
DTYNKVTHLN EDDKAHLRQL QLQISEMSDL RCLFVLLLRR FNPSIHSKQY LQDLVVTNHI 

       790        800        810        820        830        840 
LLLILDSSAK LGGCQTIRLS EHITQFATLE VMHYYGILLE DFNNNGEFVN DCIFTMMHHI 

       850        860        870        880        890        900 
GGDLGQIGVL FQPIILKTYS RIWEADYELC DDWSDLIEYV IHKFMNTPPK SPLTIPTTSL 

       910        920        930        940        950        960 
TEMTKEHNQE HTVCSWSQEE MDTLYWYYVQ SKKNNDIVGK IVKLFSNNGN KLKTRISIIQ 

       970        980        990       1000       1010       1020 
QLLQQDIITL LEYDDLMKFE DAEYQRTLLT TPTSATTESG IEIKECAYGK PSDDVQILLD 

      1030       1040       1050       1060       1070       1080 
LIIKENKAQH LLWLQRILIE CCFVKLTLRS GLKVPEGDHI MEPVAYHCIC KQKSIPVVQW 

      1090       1100       1110       1120       1130       1140 
NNEQSTTMLY QPFVLLLHKL GIQLPADAGS IFARIPDYWT PETMYGLAKK LGPLDKLNLK 

      1150       1160       1170       1180       1190       1200 
FDASELEDAT ASSPSRYHHT GPRNSLSSVS SLDVDLGDTE ELALIPEVDA AVEKAHAMAS 

      1210       1220       1230       1240       1250       1260 
TPSPSEIFAV PKTKHCNSII RYTPDPTPPV PNWLQLVMRS KCNHRTGPSG DPSDCVGSSS 

      1270       1280       1290       1300       1310       1320 
TTVDDEGFGK SISAATSQAA STSMSTVNPT TTLSLNMLNT FMGSHNENSS SSGCGGTVSS 

      1330       1340       1350       1360       1370       1380 
LSMVALMSTG AAGGGGNTSG LEMDVDASMK SSFERLEVNG SHFSRANNLD QEYSAMVASV 

      1390       1400       1410       1420 
YEKEKELNSD NVSLASDLTR MYVSDEDDRL ERTEIRVPHY H 

« Hide

Isoform A [UniParc].

Checksum: 5A2E721D10F0B017
Show »

FASTA1,389155,666
Isoform C [UniParc].

Checksum: 7E89D53409433327
Show »

FASTA914103,456
Isoform B [UniParc].

Checksum: 1DE5DDC5DE514902
Show »

FASTA1,398156,368

References

« Hide 'large scale' references
[1]"Positional cloning and sequence analysis of the Drosophila clock gene, timeless."
Myers M.P., Wager-Smith K., Wesley C.S., Young M.W., Sehgal A.
Science 270:805-808(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]"Comparison of chromosomal DNA composing timeless in Drosophila melanogaster and D. virilis suggests a new conserved structure for the TIMELESS protein."
Myers M.P., Rothenfluh A., Chang M., Young M.W.
Nucleic Acids Res. 25:4710-4714(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM B).
[3]"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.
[4]"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.
[5]"Conceptual translation of timeless reveals alternative initiating methionines in Drosophila."
Rosato E., Trevisan A., Sandrelli F., Zordan M., Kyriacou C.P., Costa R.
Nucleic Acids Res. 25:455-458(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-53 (ISOFORMS A/D/C), ALTERNATIVE INITIATION.
Strain: Canton-S, CO-TG14, CO-TG20, PER+, PER01 and PERS.
[6]"A Drosophila full-length cDNA resource."
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E.
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 57-1421 (ISOFORM C), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1138-1421 (ISOFORMS A/B/D).
Strain: Berkeley.
Tissue: Head.
[7]"Conserved regions of the timeless (tim) clock gene in Drosophila analyzed through phylogenetic and functional studies."
Ousley A., Zafarullah K., Chen Y., Emerson M., Hickman L., Sehgal A.
Genetics 148:815-825(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 243-303 (ISOFORMS B/C/D).
[8]"Isolation of timeless by PER protein interaction: defective interaction between timeless protein and long-period mutant PERL."
Gekakis N., Saez L., Delahaye-Brown A.M., Myers M.P., Sehgal A., Young M.W., Weitz C.J.
Science 270:811-815(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U37018 mRNA. Translation: AAC46920.1.
AF032401, AF032400 Genomic DNA. Translation: AAB94890.1.
AE014134 Genomic DNA. Translation: AAF51097.1.
AE014134 Genomic DNA. Translation: AAF51098.4.
AE014134 Genomic DNA. Translation: AAN10371.2.
AE014134 Genomic DNA. Translation: AAN10372.2.
Y09930 Genomic DNA. No translation available.
Y09931 Genomic DNA. No translation available.
Y09932 Genomic DNA. No translation available.
Y09933 Genomic DNA. No translation available.
Y09934 Genomic DNA. No translation available.
Y09935 Genomic DNA. No translation available.
AY058278 mRNA. Translation: AAL13507.1. Sequence problems.
BT001424 mRNA. Translation: AAN71179.1. Different initiation.
AF038501 Genomic DNA. Translation: AAB94929.1.
PIRA57655.
RefSeqNP_001188687.2. NM_001201758.2.
NP_722912.3. NM_164540.4.
NP_722913.3. NM_164541.5.
NP_722914.3. NM_164542.4.
UniGeneDm.2663.

3D structure databases

ProteinModelPortalP49021.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid59781. 7 interactions.
DIPDIP-29425N.
MINTMINT-344208.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID33571.
KEGGdme:Dmel_CG3234.
UCSCCG3234-RA. d. melanogaster. [P49021-1]

Organism-specific databases

CTD107698.
FlyBaseFBgn0014396. tim.

Phylogenomic databases

eggNOGNOG257888.
InParanoidP49021.
KOK12074.
OrthoDBEOG7SXW2F.

Gene expression databases

BgeeP49021.

Family and domain databases

InterProIPR006906. Timeless.
[Graphical view]
PfamPF04821. TIMELESS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSARHGEF5. drosophila.
GenomeRNAi33571.
NextBio784249.

Entry information

Entry nameTIM_DROME
AccessionPrimary (citable) accession number: P49021
Secondary accession number(s): O44380 expand/collapse secondary AC list , Q8I037, Q95U67, Q9VQR6, Q9VQR7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: July 15, 1999
Last modified: April 16, 2014
This is version 120 of the entry and version 2 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