dTIM, rit, tim1, Ritsu
transcription factor - novel with pas domain - photoperiod response - partners the transcription factor Period - involved in mating behavior, DNA replication and larval phototaxis
Please see the JBrowse view of Dmel\tim for information on other features
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AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.
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
Gene model reviewed during 6.33
5.2 (compiled cDNA)
~180 (kD)
180-190 (kD)
1389, 1122 (aa); 156 (kD predicted)
Forms a heterodimer with period (PER); the complex then translocates into the nucleus.
Phosphorylated with a circadian rhythmicity.
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.
The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).
Comment: tim expression is significantly higher at ZT16 compared to ZT4.
Comment: cyclical, peak ZT13-16
Comment: displays circadian cycling
Comment: displays circadian cycling
Comment: circadian oscillating expression
Expression oscillates with the circadian cycle and peaks at ZT16, with the peak becoming less pronounced as flies age. Both the relative amount of mRNA and the strength of the peak are less in bodies compared to heads, and the rise to peak expression is more gradual.
Expressed cyclically in the adult fat body.
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 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.
Comment: Expression strong at night, but weak during the day.
Comment: Expression weak at night, but strong during the day.
Comment: circadian oscillating expression
Comment: circadian oscillating expression
Comment: circadian oscillating expression
Comment: circadian oscillating expression
Comment: DNa are found 15-30um anterior of DN1.
Comment: Authors state they find weak tim staining in glial cells, but do not detail which.
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 ScerGAL4tim.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.
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.
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.
Comment: Assayed at ZT23
Comment: Authors state tim-gal4 is known to express in all clock neurons.
Comment: medium expression
Comment: faint expression
JBrowse - Visual display of RNA-Seq signals
View Dmel\tim in JBrowse
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
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 JBrowse for alignment of the cDNAs and ESTs to the gene model.
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.
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.
tim may be linked to the rest homeostatic mechanism.
Mutations in tim abolish circadian rhythms in olfactory responses.
timrit lengthens circadian period in a temperature-dependent manner.
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.
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.
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.
Identification: as a protein that interacts specifically with per protein in a yeast two-hybrid assay.
"Maps to the left of cl" was stated as tentative.
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.
Mutations in tim produce arrhythmia for emergence of adult flies from the pupae and locomotor activity in adults.
Mutations of tim produce arrhythmic behaviour.
Source for merge of: tim rit
'ritsu' means rhythm in Japanese.
