Timeless timeless circadian clock 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Timelessprovided by MGI
Official Full Name: timeless circadian clock 1provided by MGI
Primary source: MGI:MGI:1321393
See related: Ensembl:ENSMUSG00000039994 AllianceGenome:MGI:1321393
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: tim; Debt69
Summary: The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]
Expression: Broad expression in CNS E11.5 (RPKM 6.3), limb E14.5 (RPKM 3.8) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 D3; 10 76.49 cM

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (128067932..128088810)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (128232063..128252941)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling.
Title: Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling.
The mutation prevents TIM accumulation in the nucleus and has altered affinity for CRY2.
Title: TIMELESS mutation alters phase responsiveness and causes advanced sleep phase.
The obtained results suggest that Tim is expressed in neuronal tissues in a spatiotemporally regulated manner and involved in developmental stage-specific neuronal functions.
Title: Morphological characterization of mammalian timeless in the mouse brain development.
The Phosphorylation of timeless protein by Hck and Fyn induced Tim ubiquitylation on K48 and subsequent degradation, while c-Src and c-Yes led to K63-linked ubiquitylation and Tim accumulation within cells.
Title: Individual Src-family tyrosine kinases direct the degradation or protection of the clock protein Timeless via differential ubiquitylation.
Data indicate that RNAi-mediated knockdown of TIMELESS (TIM) in NIH3T3 and U2OS cells shortens the period by 1 hour and diminishes DNA damage-dependent phase advancing.
Title: Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock.
A new function for Tim in the coordination of ES cell differentiation and in developmental apoptosis.
Title: An unexpected role for the clock protein timeless in developmental apoptosis.
The tim-Tipin dysfunction creates an indispensable reliance on the ATR-Chk1 pathway for continued DNA synthesis.
Title: Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis.
A polyclonal antibody was generated to tim and its distribution was studied during lung development.
Title: Timeless in lung morphogenesis.
mTIM promotes the nuclear localization of TIPIN, and TIPIN is capable of regulating mTIM activity by disrupting the ability of mTIM to form homo-multimeric complexes
Title: Tipin, a novel timeless-interacting protein, is developmentally co-expressed with timeless and disrupts its self-association.
TIM and Tipin are functional orthologs of their replisome-associated yeast counterparts capable of coordinating
Title: Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (1) 1 citation
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Mip (e-PCR), detects polymorphism
- UniSTS:143872

RH126161 (e-PCR)
- UniSTS:162872

AB019001 (e-PCR)
- UniSTS:163489

U27502 (e-PCR)
- UniSTS:180129

NoName (e-PCR)
- UniSTS:236486

Timeless (e-PCR), detects polymorphism
- UniSTS:144624

AI323353 (e-PCR)
- UniSTS:208626

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA damage response	ISO Inferred from Sequence Orthology more info
involved_in DNA damage response	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in DNA replication checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within branching involved in ureteric bud morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in branching involved in ureteric bud morphogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within branching morphogenesis of an epithelial tube	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell cycle phase transition	IEA Inferred from Electronic Annotation more info
involved_in cell cycle phase transition	ISO Inferred from Sequence Orthology more info
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in cellular response to bleomycin	ISO Inferred from Sequence Orthology more info
involved_in cellular response to bleomycin	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to cisplatin	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cisplatin	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to hydroxyurea	ISO Inferred from Sequence Orthology more info
involved_in cellular response to hydroxyurea	ISS Inferred from Sequence or Structural Similarity more info
involved_in circadian rhythm	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within embryo development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lung development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in morphogenesis of an epithelium	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of circadian rhythm	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of double-strand break repair	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of double-strand break repair	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of double-strand break repair via homologous recombination	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of double-strand break repair via homologous recombination	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of circadian rhythm	ISO Inferred from Sequence Orthology more info
involved_in replication fork arrest	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in chromatin	IEA Inferred from Electronic Annotation more info
located_in chromatin	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of replication fork protection complex	IBA Inferred from Biological aspect of Ancestor more info
located_in site of double-strand break	ISO Inferred from Sequence Orthology more info
located_in site of double-strand break	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: protein timeless homolog

Names: mTim; timeless homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001136082.2 → NP_001129554.1 protein timeless homolog isoform 1

See identical proteins and their annotated locations for NP_001129554.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) uses an alternate in-frame splice site in the 3' coding region, compared to variant 4. This variant is distinct from but the same length as variant 3. The resulting isoform (1) lacks one aa near the C-terminus, compared to isoform 2, and is distinct from isoform 3.

Source sequence(s)

BC052884, BC082770

Consensus CDS

CCDS48725.1

UniProtKB/Swiss-Prot

Q9R1X4

Related

ENSMUSP00000100876.2, ENSMUST00000105242.8

Conserved Domains (3) summary

pfam05029
Location:722 → 1189

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:25 → 284

TIMELESS; Timeless protein

cl10555
Location:539 → 611

Chorismate_bind; chorismate binding enzyme
NM_001164080.1 → NP_001157552.1 protein timeless homolog isoform 3

See identical proteins and their annotated locations for NP_001157552.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region, compared to variant 4. The resulting isoform (3) lacks one aa near the C-terminus, compared to isoform 2.

Source sequence(s)

AK153838, BC052884, BC082770

Consensus CDS

CCDS48724.1

UniProtKB/TrEMBL

Q3U574

Related

ENSMUSP00000100878.2, ENSMUST00000105244.8

Conserved Domains (3) summary

pfam05029
Location:722 → 1189

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:25 → 284

TIMELESS; Timeless protein

cl10555
Location:539 → 611

Chorismate_bind; chorismate binding enzyme
NM_001164081.1 → NP_001157553.1 protein timeless homolog isoform 2

See identical proteins and their annotated locations for NP_001157553.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (2). Both variants 2 and 4 encode the same isoform.

Source sequence(s)

BC052884, BC082770, CJ088470

Consensus CDS

CCDS24266.1

UniProtKB/Swiss-Prot

Q63ZX9, Q6P204, Q6PDL4, Q7TPV8, Q8R0Q2, Q9R1X4, Q9R268, Q9Z0E7

Related

ENSMUSP00000058021.5, ENSMUST00000055539.11

Conserved Domains (2) summary

pfam05029
Location:722 → 1190

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:25 → 284

TIMELESS; Timeless protein
NM_011589.2 → NP_035719.1 protein timeless homolog isoform 2

See identical proteins and their annotated locations for NP_035719.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) represents use of an alternate promoter and 5' UTR, compared to variant 4. Both variants 2 and 4 encode the same isoform (2).

Source sequence(s)

AF098161, BC082770

Consensus CDS

CCDS24266.1

UniProtKB/Swiss-Prot

Q63ZX9, Q6P204, Q6PDL4, Q7TPV8, Q8R0Q2, Q9R1X4, Q9R268, Q9Z0E7

Related

ENSMUSP00000100879.3, ENSMUST00000105245.3

Conserved Domains (2) summary

pfam05029
Location:722 → 1190

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:25 → 284

TIMELESS; Timeless protein

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000076.7 Reference GRCm39 C57BL/6J

Range

128067932..128088810

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030245050.1 → XP_030100910.1 protein timeless homolog isoform X6

Conserved Domains (1) summary

pfam05029
Location:365 → 833

TIMELESS_C; Timeless protein C terminal region
XM_030245049.2 → XP_030100909.1 protein timeless homolog isoform X4

Conserved Domains (2) summary

pfam05029
Location:783 → 1249

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:86 → 345

TIMELESS; Timeless protein
XM_006513582.3 → XP_006513645.1 protein timeless homolog isoform X3

Conserved Domains (2) summary

pfam05029
Location:783 → 1250

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:86 → 345

TIMELESS; Timeless protein
XM_006513581.5 → XP_006513644.1 protein timeless homolog isoform X2

Conserved Domains (2) summary

pfam05029
Location:783 → 1250

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:86 → 345

TIMELESS; Timeless protein
XM_006513580.3 → XP_006513643.1 protein timeless homolog isoform X1

Conserved Domains (2) summary

pfam05029
Location:783 → 1251

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:86 → 345

TIMELESS; Timeless protein
XM_006513583.3 → XP_006513646.1 protein timeless homolog isoform X5

See identical proteins and their annotated locations for XP_006513646.1

UniProtKB/Swiss-Prot

Q63ZX9, Q6P204, Q6PDL4, Q7TPV8, Q8R0Q2, Q9R1X4, Q9R268, Q9Z0E7

Conserved Domains (2) summary

pfam05029
Location:722 → 1190

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:25 → 284

TIMELESS; Timeless protein