General Information
Symbol
Dmel\tim
Species
D. melanogaster
Name
timeless
Annotation Symbol
CG3234
Feature Type
FlyBase ID
FBgn0014396
Gene Model Status
Stock Availability
Gene Snapshot
Timeless (Tim) is a key component of the Tim-per complex, required for the production of circadian rhythms. It is involved in mating behavior, DNA replication and larval phototaxis. [Date last reviewed: 2016-06-30]
Also Known As
dTIM, rit, tim1, Ritsu
Genomic Location
Cytogenetic map
Sequence location
2L:3,493,986..3,508,119 [-]
Recombination map
2-10
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
GO Summary Ribbons
Families, Domains and Molecular Function
Gene Group Membership (FlyBase)
Protein Family (UniProt, Sequence Similarities)
Belongs to the timeless family. (P49021)
Protein Domains/Motifs
Molecular Function (see GO section for details)
Summaries
UniProt Contributed Function Data
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.
(UniProt, P49021)
Interactive Fly
transcription factor - novel with pas domain - photoperiod response - partners the transcription factor Period - involved in mating behavior, DNA replication and larval phototaxis
Gene Model and Products
Number of Transcripts
9
Number of Unique Polypeptides
8

Please see the GBrowse view of Dmel\tim or the JBrowse view of Dmel\tim for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Gene model reviewed during 6.01
Annotated transcripts do not represent all supported alternative splices within 5' UTR.
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
Gene model reviewed during 5.46
Gene model reviewed during 5.56
Gene model reviewed during 6.08
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0077567
5073
1398
FBtr0333252
5077
1397
FBtr0333253
5641
1131
FBtr0333254
3136
890
FBtr0333255
3525
891
FBtr0333256
5404
1398
FBtr0333258
5020
1366
FBtr0333259
5214
1099
FBtr0445397
5073
1421
Additional Transcript Data and Comments
Reported size (kB)
5.2 (compiled cDNA)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0077256
156.4
1398
4.89
FBpp0305450
156.3
1397
4.87
FBpp0305451
128.2
1131
5.11
FBpp0305452
100.5
890
4.88
FBpp0305453
100.6
891
4.91
FBpp0305454
156.4
1398
4.89
FBpp0305456
152.8
1366
4.94
FBpp0305457
124.7
1099
5.22
FBpp0401565
159.2
1421
5.01
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

1398 aa isoforms: tim-PB, tim-PP
Additional Polypeptide Data and Comments
Reported size (kDa)
180-190 (kD)
1389, 1122 (aa); 156 (kD predicted)
Comments
External Data
Subunit Structure (UniProtKB)
Forms a heterodimer with period (PER); the complex then translocates into the nucleus.
(UniProt, P49021)
Post Translational Modification
Phosphorylated with a circadian rhythmicity.
(UniProt, P49021)
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\tim using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (36 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
inferred from physical interaction with FLYBASE:per; FB:FBgn0003068
inferred from physical interaction with FLYBASE:cry; FB:FBgn0025680
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
traceable author statement
non-traceable author statement
Biological Process (26 terms)
Terms Based on Experimental Evidence (16 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:jet; FB:FBgn0031652
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by CACAO )
inferred from mutant phenotype
(assigned by CACAO )
Terms Based on Predictions or Assertions (14 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
traceable author statement
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000533816
(assigned by GO_Central )
traceable author statement
non-traceable author statement
non-traceable author statement
traceable author statement
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
traceable author statement
non-traceable author statement
Cellular Component (6 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
traceable author statement
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000533813
(assigned by GO_Central )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
expression microarray
Stage
Tissue/Position (including subcellular localization)
Reference
adult brain

Comment: tim expression is significantly higher at ZT16 compared to ZT4.

in situ
Stage
Tissue/Position (including subcellular localization)
Reference
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
RNase protection, primer extension, SI map
Stage
Tissue/Position (including subcellular localization)
Reference
RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
adult oenocyte

Comment: displays circadian cycling

adult fat body

Comment: displays circadian cycling

Additional Descriptive Data
The levels of tim transcript oscillate throughout the day in a circadian fashion, similarly to per but in contrast to inc. Expression of tim is highest between ZT10 to ZT20.
tim is expressed in adult oenocytes and shows a sinusoidal expression pattern with a peak at night and a trough during the day.
tim mRNA shows robust circadian cycling in the pacemaker neuron of wildtype flies.
tim and vri transcripts are expressed in the same cells in the brain, the photoreceptor cells and two clusters in the brain corresponding to the ventral and dorsal lateral neurons (the pacemaker cells). Clock-dependent cycling of vri and tim transcripts is also observed in adult bodies.
tim transcripts show circadian cycling with a pattern that is antiphase to that of Clk transcripts. Peak values of tim transcripts occur in the early night.
tim transcripts are expressed in photoreceptor cells in the eye. They are also expressed in a discreet pattern in the brain and are found at the highest levels in the lateral neurons.
tim transcript levels in adult flies are not affected by exposure to light.
tim RNA levels were measured in adult heads at 4 hour intervals. tim RNA accumulation follows a circadian rhythm, and the oscillation patterns of tim and per RNA match. The maintenance of the circadian rhythmic accumulation of tim RNA is dependent on the presence of per and tim proteins. In flies reared in a 12 h light - 12 hr dark cycle, tim expression is highest at the end of the day, and lowest in early dawn.
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
inferred from author statements
Stage
Tissue/Position (including subcellular localization)
Reference
glial cell | subset

Comment: Authors state they find weak tim staining in glial cells, but do not detail which.

mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
tim protein starts being expressed in the embryonic brain at stage 12, extending gradually to 160 neurons at stage 16; 130 of those also express Scer\GAL4tim.PE. tim-positive neurons are found throughout the brain but with more cells located rostrally. Around 20 cells co-express per and tim. These cells are located in the lateral protocerebrum, close to where the lateral and dorsomedial larval clock neurons are found. Expression of tim in the ventral nerve cord starts at stage 12 in a few neurons in the anterior commissure. The number of midline and lateral labeled cells increases until stage 16, when per is detected in 8 midline cells and 11 pairs of lateral cells per segment. The lateral clusters of neurons express tim more strongly than the glial midline cells. More cells are detected in the thoracic segments than in the abdominal ones. Co-expression with en shows that almost all of the tim cells are anterior to the en domain.
tim levels are seen to strongly deplete in pacemaker neurons after lights on.
At 1 hour before lights on in an LD cycle, tim is predominantly nuclear localized, close to the nuclear membrane, but slightly centrifugal (lateral) to the per localization. tim protein levels are highest 3hrs before lights on and lowest 12hrs later.
Observed at ZT00, 06, 12 and 18, tim protein shows oscillation in the LP neurons and DN1a neurons under a 12:12 LD cycle.
tim protein shows strong oscillations under LD conditions, with a peak in the night and a rapid decrease at lights on.
By ZT2 tim is no longer seen in the nucleus of the l-LNvs. Significant levels of tim are seen in the cytoplasm by ZT18, 6 hours after lights off, and starts to appear in the nucleus by ZT19, becoming predominantly nuclear by ZT21. In the s-LNvs, tim was seen to be largely restricted to the cytoplasm through to ZT20, but becomes predominantly nuclear by ZT24.
Expression levels of tim cycle in Malpighian tubules in a circadian pattern.
tim protein is coexpressed with Pdf protein in larval lateral neurons.
Subcellular localization of tim protein in the larval LNs, DN1s and DN2s is both nuclear and cytoplasmic at the peak-expression time point. tim protein colocalizes with per protein. In the DN2s, tim expression was found to be in antiphase compared to the LNs and DN1.
In adult head sections, tim protein is detected in the nuclei of photoreceptor cells. This nuclear localization does not occur in per01 flies, and is thus dependent on the presence of per protein. Additional expression is detected in some lateral neurons of the protocerebrum, and glial cells in the lamina and medulla of the optic lobes. The peak of tim protein expression lags behind that of tim transcript expression.
Rhythmic accumulation of tim protein was detected in Western blots of adult head protein, whether the flies were kept in a LD 12:12 cycle, or in total darkness. In flies kept in a LD 12:12 cycle, there was an upward shift in the mobility of tim protein late at night, and peak accumulation was seen at the 6th hour of darkness. Immunolocalization to adult head sections shows that tim protein accumulates rhythmically in nuclei of photoreceptor cells and in nuclei and cytoplasm of pacemaker cells of the brain. The putative pacemakers, also called "lateral neurons", are clusters of neurons in the lateral protocerebrum. Lower levels of tim protein are detected in cells dispersed throughout the optic lobes.
Marker for
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
Reporter: P{GAL4-tim.E}
Stage
Tissue/Position (including subcellular localization)
Reference
CNS glial cell | subset

Comment: At the border between adjacent neuropils

pacemaker neuron

Comment: Authors state tim-gal4 is known to express in all clock neurons.

glial cell of adult brain

Comment: strong expression

eye

Comment: medium expression

Reporter: P{UAS-tim-GAL4}
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\tim in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 13-16
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 29 )
Transgenic Constructs ( 33 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of tim
Allele of tim
Mutagen
Associated Transgenic Construct
Stocks
Transgenic constructs containing regulatory region of tim
GAL4 construct
vital-reporter construct
Name
Expression Data
reporter construct
Deletions and Duplications ( 8 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
6 of 15
Yes
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
5 of 15
Yes
No
Rattus norvegicus (Norway rat) (1)
5 of 13
Yes
No
Xenopus tropicalis (Western clawed frog) (1)
4 of 12
Yes
No
Danio rerio (Zebrafish) (1)
5 of 15
Yes
No
Caenorhabditis elegans (Nematode, roundworm) (1)
3 of 15
Yes
No
Arabidopsis thaliana (thale-cress) (1)
1 of 9
Yes
No
Saccharomyces cerevisiae (Brewer's yeast) (1)
3 of 15
Yes
No
Schizosaccharomyces pombe (Fission yeast) (1)
2 of 12
Yes
No
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091900Y8 )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091502FB )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W018Z )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0173 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G01UQ )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Human Disease Model Data
FlyBase Human Disease Model Reports
    Alleles Reported to Model Human Disease (Disease Ontology)
    Download
    Models ( 0 )
    Allele
    Disease
    Evidence
    References
    Interactions ( 0 )
    Allele
    Disease
    Interaction
    References
    Comments ( 0 )
     
    Human Orthologs (via DIOPT v7.1)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    Complementation?
    Transgene?
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Interactions Browser

    Please look at the Interaction Group reports for full details of the physical interactions
    RNA-protein
    Interacting group
    Assay
    References
    RNA-RNA
    Interacting group
    Assay
    References
    protein-protein
    Interacting group
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    esyN Network Key:
    Suppression
    Enhancement

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Forms a heterodimer with period (PER); the complex then translocates into the nucleus.
    (UniProt, P49021 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    Pathways
    Gene Group - Pathway Membership (FlyBase)
    External Data
    Linkouts
    KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2L
    Recombination map
    2-10
    Cytogenetic map
    Sequence location
    2L:3,493,986..3,508,119 [-]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    23F6-23F6
    Limits computationally determined from genome sequence between P{EP}ThorEP818&P{lacW}Thork07736 and P{PZ}oddrF111&P{PZ}for06860
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    23F5-23F6
    Experimentally Determined Recombination Data
    Notes
    No recombinants between timrit and tim01 occurred in 700 progeny of the transheterozygous females.
    Maps near or to the left of cl.
    Mapping based on 2 recombinants/1248 tested chromosomes.
    Stocks and Reagents
    Stocks (17)
    Genomic Clones (22)
    cDNA Clones (50)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequences
    BDGP DGC clones
    Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    Antibody Information
    Laboratory Generated Antibodies
    Commercially Available Antibodies
     
    Other Information
    Relationship to Other Genes
    Source for database identify of
    Source for database merge of
    Source for merge of: tim rit
    Additional comments
    Other Comments
    Duplicate transcripts identified and eliminated during the migration of annotations from the release 5 genome assembly to the release 6 assembly.
    Gene expression is increased in response to the presence of either one or two copies of Scer\GAL4hs.PB.
    Shows particularly robust cycling of transcription in adult heads, as assessed by expression analysis using high density oligonucleotide arrays with probe generated during three 12-point time course experiments over the course of 6 days. Shows significant change of expression pattern in circadian mutant background; increased expression in per01, tim01 and decreased expression in ClkJrk background.
    Identified as one of 10 highest fold cycling genes as assessed by expression analysis using high density oligonucleotide arrays with probe generated from adult heads harvested over six time points over the course of a day. Identified in S2/cycloheximide assay as a direct target of Clk mediated transcriptional regulation.
    per has a role in circadian mating rhythm regulation.
    Maintenance of the per-tim feedback loop is not an absolute requirement for behavioral rhythms, but cyclic expression of the two proteins is essential.
    Excretory organs exhibit autonomous per and tim cycling.
    tim may be linked to the rest homeostatic mechanism.
    Light and post-transcriptional regulation play major roles in defining the temporal properties of the per and tim protein curves. The lag between mRNA and protein accumulation is unecessary for the feedback regulation of per and tim protein on per and tim transcription.
    CrebB-17A supports cycling of the per/tim oscillator.
    The cry and tim gene products physically interact in a yeast two hybrid assay in a light-dependent fashion.
    The cry gene product blocks the function of the per/tim heterodimeric complex in a light-dependent fashion.
    Mutations in tim abolish circadian rhythms in olfactory responses.
    Daily cycles in the association of per and tim proteins with the Clk-cyc complex may contribute to rhythmic expression of per and tim.
    timrit lengthens circadian period through suppression of per protein cycling and nuclear localization.
    timrit lengthens circadian period in a temperature-dependent manner.
    tim is degraded through a ubiquitin-proteasome mechanism. tim is ubiquitinated in response to light in cultured cells.
    tim increases per mRNA levels through a post-transcriptional mechanism.
    Transcription of per and tim, inhibitors of Clk, is induced by Clk.
    The function of dco may be to reduce the stability and thus the level of accumulation of monomeric per proteins, promoting the delay between per/tim transcription and the function of the per/tim protein complex, which is essential for molecular rhythmicity.
    Heat pulses at all times in a daily cycle elicited dramatic and rapid decreases in the levels of per and tim proteins, the proteins can be independently degraded by heat pulses. These two modalities produce markedly different long term effects on the circadian time-keeping mechanism. Heat-induced phase delays in behavioural rhythms are accompanied by long-term delays in the per and tim biochemical oscillations. Heat pulses in the late night elicit transient and rapid increases in the speed of the per-tim cycles. The timing of per and tim mRNA cycles is perturbed by heat pulses in a manner consistent with the direction and magnitude of the behavioural phase shift.
    The initiating Met of Dsim\tim and Dyak\tim appears to lie downstream of the one proposed to encode the translational start in tim, thereby truncating the N-terminus by 23 amino acids. Sequencing the 5' fragment in tim reveals a polymorphism which strongly suggests that the originally proposed site cannot be utilised in some individuals and these flies with initiate translation of tim at the downstream ATG.
    Post-transcriptional circadian regulation serves to ensure proper circadian fluctuations of clock gene expression.
    tim mediates light-induced resetting of the circadian clock. The effects of light on tim appear to be post-transcriptional.
    Cyclic expression of tim protein lags behind that of tim RNA by several hours. Nuclear expression of tim depends on per. The expression of tim, but not per, is rapidly reduced by light.
    Photic stimuli perturb the timing of the per protein and mRNA cycles in a manner consistent with the direction and magnitude of the phase shift. The tim protein interacts with per in vivo, and the association is rapidly decreased by light. The disruption of the per-tim complex in the cytoplasm is accompanied by a delay in per phosphorylation and nuclear entry and disruption in the nucleus by an advance in per phosphorylation and disappearance.
    Light inhibits the level and phosphorylation status of per and tim proteins, this then delays the negative feedback circuit (in which per or the per-tim complex participates) and extends the RNA profiles.
    The tim and per proteins physically interact and the timing of their association and nuclear localization promotes cycles of per and tim transcription through an autoregulatory feedback loop.
    tim couples the per-tim pacemaker to the environment: the tim gene product is rapidly degraded on exposure to light.
    The identification of a period-altering tim allele provides further evidence that tim is a major component of the clock, and the allele-specific interactions with per provide evidence that the per/tim heterodimer is a unit of circadian function.
    tim and per accumulate in the cytoplasm when independently expressed in S2 cells and move to the nucleus when coexpressed. Domains of per and tim have been identified that block nuclear localisation of the monomeric proteins. In vitro protein interaction studies indicate that the sequence inhibiting the nuclear accumulation of per forms a binding site for tim. Results indicate a mechanism for controlled nuclear localisation in which suppression of cytoplasmic localisation is accomplished by direct interaction of per and tim.
    per and tim are in a large protein complex, they are heterodimeric partners. Light causes tim protein degradation.
    Identification: as a protein that interacts specifically with per protein in a yeast two-hybrid assay.
    The interaction between the tim and per products determines the duration of part of the circadian cycle.
    The interaction between the tim and per products determines the timing of per nuclear entry.
    "Maps to the left of cl" was stated as tentative.
    tim and per interact; both are required for circadian rhythms.
    Absence of tim sequence similarity to the PER dimerization motif (PAS) indicates that direct interaction between the per and tim products would require a heterotypic protein association.
    tim suppresses circadian oscillations of per abundance and phosphorylation in light/dark cycles, depresses levels of per and blocks nuclear localisation of a per reporter gene due to a primary affect on per expression at the post-transcriptional level. Constant light has no effect on per in tim flies.
    Mutations of tim lead to loss of circadian rhythms.
    The accumulation of tim RNA follows a circadian rhythm, the phase and period of which are indistinguishable from those reported for per. The tim RNA oscillations are dependent on the presence of per and tim proteins. The cyclic expression of tim appears to dictate the timing of per protein accumulation and nuclear localization, suggesting that tim promotes circadian rhythms of per and tim transcription by restricting per RNA and protein accumulation to separate times of day.
    tim mutants suppress the circadian oscillation of per transcript.
    Mutations in tim produce arrhythmia for emergence of adult flies from the pupae and locomotor activity in adults.
    tim mutants suppress the circadian oscillation of per transcripts. tim is required for nuclear localisation of per protein.
    Mutations of tim produce arrhythmic behaviour.
    Origin and Etymology
    Discoverer
    Etymology
    'ritsu' means rhythm in Japanese.
    Identification
    External Crossreferences and Linkouts ( 89 )
    Sequence Crossreferences
    NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
    GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
    GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
    UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
    UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
    Other crossreferences
    BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
    InterPro - A database of protein families, domains and functional sites
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center cDNA clones
    DroID - A comprehensive database of gene and protein interactions.
    DRSC - Results frm RNAi screens
    Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
    FLIGHT - Cell culture data for RNAi and other high-throughput technologies
    FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
    FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
    Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
    Flygut - An atlas of the Drosophila adult midgut
    FlyMine - An integrated database for Drosophila genomics
    Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
    Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    KEGG Genes - Molecular building blocks of life in the genomic space.
    KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    modMine - A data warehouse for the modENCODE project
    Synonyms and Secondary IDs (19)
    Reported As
    Symbol Synonym
    tim
    (Boomgarden et al., 2019, Baik et al., 2018, Filošević et al., 2018, Giebultowicz, 2018, Lamba et al., 2018, Luo et al., 2018, Nagy et al., 2018, Noreen et al., 2018, Olesnicky et al., 2018, Top et al., 2018, Young, 2018, Zhang et al., 2018, Zonato et al., 2018, Abruzzi et al., 2017, Agrawal et al., 2017, Allen et al., 2017, He et al., 2017, Jiang et al., 2017, Li et al., 2017, Liu et al., 2017, Park et al., 2017, Selcho et al., 2017, Vaccaro et al., 2017, Zhao and Karpac, 2017, Chen and Rosbash, 2016, Cho et al., 2016, Di Cara and King-Jones, 2016, Fu et al., 2016, Kim et al., 2016, Kučerová et al., 2016, Lazopulo and Syed, 2016, Lone et al., 2016, Maurer et al., 2016, Mezan et al., 2016, Nikhil et al., 2016, Schiesari et al., 2016, Andreazza et al., 2015, Chen et al., 2015, Donelson and Sanyal, 2015, Gene Disruption Project members, 2015-, Giebultowicz and Long, 2015, Gill et al., 2015, Green et al., 2015, Grotewiel and Bettinger, 2015, Head et al., 2015, Jang et al., 2015, Jaumouillé et al., 2015, Kidd et al., 2015, Klichko et al., 2015, Lerner et al., 2015, Maguire and Sehgal, 2015, Merbitz-Zahradnik and Wolf, 2015, Montelli et al., 2015, Moskalev et al., 2015, Tomita et al., 2015, Zhao et al., 2015, Zwarts et al., 2015, Ashwal-Fluss et al., 2014, FlyBase Genome Annotators, 2014, Goda et al., 2014, Lamba et al., 2014, Lee et al., 2014, Liu and Zhao, 2014, Liu et al., 2014, Pegoraro et al., 2014, Seluzicki et al., 2014, Taylor et al., 2014, Weiss et al., 2014, Zheng et al., 2014, Beckwith et al., 2013, Erion and Sehgal, 2013, Garbe et al., 2013, Górska-Andrzejak, 2013, Itoh et al., 2013, Krupp et al., 2013, Kwon et al., 2013, Lee et al., 2013, Li and Rosbash, 2013, Lim and Allada, 2013, Mehta and Cheng, 2013, Pohl et al., 2013, Rakshit et al., 2013, Rodriguez et al., 2013, Zhang et al., 2013, Bywalez et al., 2012, Chen et al., 2012, Grima et al., 2012, Japanese National Institute of Genetics, 2012.5.21, Kaneko et al., 2012, Ling et al., 2012, Luo and Sehgal, 2012, Luo et al., 2012, Mizrak et al., 2012, Rakshit et al., 2012, Rieger et al., 2012, Rodriguez et al., 2012, Ruben et al., 2012, Vanin et al., 2012, Xu et al., 2012, Abruzzi et al., 2011, Chen et al., 2011, Diangelo et al., 2011, DiTacchio et al., 2011, Fogle et al., 2011, Goda et al., 2011, Hara et al., 2011, Ito et al., 2011, Itoh et al., 2011, Jackson, 2011, Lamaze et al., 2011, Lim et al., 2011, Mehnert and Cantera, 2011, Saez et al., 2011, Scribner and Fathallah-Shaykh, 2011, Staiger and Koster, 2011, Stavropoulos and Young, 2011, Barth et al., 2010, Beaver et al., 2010, Blanchard et al., 2010, Fernández-Ayala et al., 2010, Fujii and Amrein, 2010, Gegear et al., 2010, Kula-Eversole et al., 2010, Li et al., 2010, Menet et al., 2010, Nagoshi et al., 2010, Ruiz et al., 2010, Sun et al., 2010, Tang et al., 2010, Wasbrough et al., 2010, Xie et al., 2010, Yoshii et al., 2010, Currie et al., 2009, Dubruille et al., 2009, Fathallah-Shaykh et al., 2009, Gong, 2009, Hung et al., 2009, Johard et al., 2009, Kadener et al., 2009, Kempinger et al., 2009, Kilman and Allada, 2009, Landskron et al., 2009, Lyons and Roman, 2009, Peschel et al., 2009, Picot et al., 2009, Sehadova et al., 2009, Yu et al., 2009, Bagheri et al., 2008, Benito et al., 2008, Dunlap, 2008, Fernandez et al., 2008, Fujii et al., 2008, Houl et al., 2008, Ito et al., 2008, Kadener et al., 2008, Kivimäe et al., 2008, Krupp et al., 2008, Lee and Edery, 2008, Lee et al., 2008, Liu and Lehmann, 2008, Lu et al., 2008, Meissner et al., 2008, Mikhaylova et al., 2008, Miura et al., 2008, Ogawa et al., 2008, Richier et al., 2008, Sathyanarayanan et al., 2008, Sekine et al., 2008, Shaik et al., 2008, Shimizu et al., 2008, Smith et al., 2008, Tanoue et al., 2008, Taylor and Hardin, 2008, T et al., 2008, Wu et al., 2008, Xu et al., 2008, Yang et al., 2008, Yoshii et al., 2008, Boothroyd et al., 2007, Dolezelova et al., 2007, Fang et al., 2007, Fang et al., 2007, Goldman and Arbeitman, 2007, Gunawan and Doyle, 2007, Hamasaka et al., 2007, Helfrich-Forster et al., 2007, Hemsley et al., 2007, Hung et al., 2007, Kadener et al., 2007, Keegan et al., 2007, Kim et al., 2007, Ko et al., 2007, Koh et al., 2007, Krupp et al., 2007, Kuczenski et al., 2007, Kurata et al., 2007, Lim et al., 2007, Lim et al., 2007, Matsumoto et al., 2007, Mehnert et al., 2007, Stoleru et al., 2007, Suh and Jackson, 2007, Tauber et al., 2007, Vosshall, 2007, Wijnen et al., 2007, Yoshii et al., 2007, Zheng et al., 2007, Chen et al., 2006, Collins et al., 2006, Dunlap, 2006, Ganguly-Fitzgerald et al., 2006, Hamasaka and Nassel, 2006, Kadener et al., 2006, Koh et al., 2006, Koh et al., 2006, Koh et al., 2006, Kula et al., 2006, Reppert, 2006, Rush et al., 2006, Seugnet et al., 2006, Shafer et al., 2006, Van Gelder, 2006, Wijnen et al., 2006, Yu and Hardin, 2006, Cyran et al., 2005, Mazzoni et al., 2005, Nitabach et al., 2005, Yoshii et al., 2005, Yuan et al., 2005, Yuan et al., 2005, Zhou et al., 2005, Jaramillo et al., 2004, Majercak et al., 2004, Preuss et al., 2004, Beaver et al., 2003, Hall, 2003, Hendricks et al., 2003, Levine et al., 2002, Levine et al., 2002, Stanewsky et al., 2002, Yoshii et al., 2002, Hendricks et al., 2001, Ivanchenko et al., 2001, Leloup and Goldbeter, 2001, Lin et al., 2001, Petri and Stengl, 2001, Gotter et al., 2000, Kaneko et al., 2000)
    Name Synonyms
    ritsu
    timeless
    (Zonato et al., 2018, Jiang et al., 2017, Li et al., 2017, Roessingh and Stanewsky, 2017, Chen and Rosbash, 2016, Di Cara and King-Jones, 2016, Mezan et al., 2016, Nikhil et al., 2016, Ou et al., 2016, Parisky et al., 2016, Andreazza et al., 2015, Chen et al., 2015, Donelson and Sanyal, 2015, Green et al., 2015, Head et al., 2015, Merbitz-Zahradnik and Wolf, 2015, Paparazzo et al., 2015, Goda et al., 2014, Zheng et al., 2014, Erion and Sehgal, 2013, Garbe et al., 2013, Górska-Andrzejak, 2013, Krupp et al., 2013, Lee et al., 2013, Lim and Allada, 2013, Rakshit et al., 2013, Thimgan et al., 2013, Bywalez et al., 2012, Kaneko et al., 2012, Linford et al., 2012, Luo et al., 2012, Rakshit et al., 2012, Rieger et al., 2012, DiTacchio et al., 2011, Lamaze et al., 2011, Mehnert and Cantera, 2011, Barth et al., 2010, Blanchard et al., 2010, Gegear et al., 2010, Li et al., 2010, Menet et al., 2010, Ruiz et al., 2010, Dubruille et al., 2009, Gong, 2009, Johard et al., 2009, Landskron et al., 2009, Lyons and Roman, 2009, Peschel et al., 2009, Picot et al., 2009, Yu et al., 2009, Bagheri et al., 2008, Dunlap, 2008, Houl et al., 2008, Kadener et al., 2008, Krupp et al., 2008, Lee and Edery, 2008, Lee et al., 2008, Lu et al., 2008, Shimizu et al., 2008, T et al., 2008, Tomaiuolo et al., 2008, Wu et al., 2008, Boothroyd et al., 2007, Fang et al., 2007, Goldman and Arbeitman, 2007, Krupp et al., 2007, Lim et al., 2007, Lim et al., 2007, Mehnert et al., 2007, Sandrelli et al., 2007, Tauber et al., 2007, Vosshall, 2007, Wijnen et al., 2007, Wu and Silverman, 2007, Kadener et al., 2006, Koh et al., 2006, Van Gelder, 2006, Yu and Hardin, 2006, Mazzoni et al., 2005, Nitabach et al., 2005, Yuan et al., 2005, Zhou et al., 2005, Jaramillo et al., 2004, Beaver et al., 2003, Hall, 2003, Hendricks et al., 2003, Levine et al., 2002, Levine et al., 2002, Stanewsky et al., 2002, Hendricks et al., 2001, Leloup and Goldbeter, 2001, Petri and Stengl, 2001, Gotter et al., 2000, Kaneko et al., 2000, Sehgal et al., 1994, Vosshall et al., 1994)
    Secondary FlyBase IDs
    • FBgn0015535
    Datasets (0)
    Study focus (0)
    Experimental Role
    Project
    Project Type
    Title
    References (733)