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Aliases for TIMELESS Gene

Aliases for TIMELESS Gene

  • Timeless Circadian Regulator 2 3 5
  • Timeless Circadian Clock 1 2 3
  • TIM1 3 4
  • HTIM 3 4
  • TIM 3 4
  • Timeless (Drosophila) Homolog 2
  • Timeless Homolog (Drosophila) 2
  • Tof1 Homolog (S. Cerevisiae) 2
  • Protein Timeless Homolog 3
  • Timeless Homolog 3
  • Tof1 Homolog 3
  • TIMELESS1 4

External Ids for TIMELESS Gene

Previous GeneCards Identifiers for TIMELESS Gene

  • GC12P056609
  • GC12M057034
  • GC12M056526
  • GC12M055097
  • GC12M056810
  • GC12M053849

Summaries for TIMELESS Gene

Entrez Gene Summary for TIMELESS Gene

  • 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. [provided by RefSeq, Feb 2014]

GeneCards Summary for TIMELESS Gene

TIMELESS (Timeless Circadian Regulator) is a Protein Coding gene. Diseases associated with TIMELESS include Vestibular Nystagmus and Warsaw Breakage Syndrome. Among its related pathways are Circadian rhythm pathway and DNA Double-Strand Break Repair. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein heterodimerization activity.

UniProtKB/Swiss-Prot for TIMELESS Gene

  • Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication and in the regulation of the circadian clock. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCK NPAS2-ARTNL/BMAL1 ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Forms a complex with TIPIN and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. Timeless promotes TIPIN nuclear localization. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules.

Additional gene information for TIMELESS Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TIMELESS Gene

Genomics for TIMELESS Gene

GeneHancer (GH) Regulatory Elements for TIMELESS Gene

Promoters and enhancers for TIMELESS Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12I056447 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 550.8 +0.3 349 2.3 HDGF CLOCK SMAD1 MLX ARNT ARID4B SIN3A DMAP1 YY1 SLC30A9 TIMELESS BAZ2A DNAJC14 NEMP1 STAT2 RN7SL809P PRIM1 ZC3H10 PYM1 CDK2
GH12I056358 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE 11.4 +89.5 89531 3.3 HDGF PKNOX1 SMAD1 ARNT ARID4B NEUROD1 SIN3A DMAP1 ZNF2 IRF4 STAT2 BAZ2A ZC3H10 NEMP1 DNAJC14 ENSG00000257303 ENSG00000258317 IL23A PAN2 RN7SL809P
GH12I056220 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 11.4 +226.5 226534 5.7 CLOCK MLX ZFP64 FEZF1 DMAP1 YBX1 YY1 SLC30A9 ZNF213 E2F8 NABP2 RNF41 NEMP1 BAZ2A PAN2 DNAJC14 ANKRD52 PHC1P1 ZBTB39 RN7SL809P
GH12I056266 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 11.4 +182.2 182222 2 HDGF PKNOX1 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 IRF4 YY1 GC12M056238 COQ10A NEMP1 PAN2 BAZ2A PHC1P1 ANKRD52 DNAJC14 SMARCC2 RN7SL809P
GH12I056464 Enhancer 1.1 Ensembl ENCODE 0.4 -15.1 -15084 0.6 ATF1 FOXA2 ARNT ARID4B ZNF2 BRCA1 ZNF48 ARID2 ZNF143 ATF7 RBMS2 MIP SPRYD4 TIMELESS
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TIMELESS on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TIMELESS gene promoter:

Genomic Locations for TIMELESS Gene

Genomic Locations for TIMELESS Gene
chr12:56,416,373-56,449,416
(GRCh38/hg38)
Size:
33,044 bases
Orientation:
Minus strand
chr12:56,810,157-56,843,200
(GRCh37/hg19)

Genomic View for TIMELESS Gene

Genes around TIMELESS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIMELESS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIMELESS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIMELESS Gene

Proteins for TIMELESS Gene

  • Protein details for TIMELESS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UNS1-TIM_HUMAN
    Recommended name:
    Protein timeless homolog
    Protein Accession:
    Q9UNS1
    Secondary Accessions:
    • B2ZAV0
    • O94802
    • Q86VM1
    • Q8IWH3

    Protein attributes for TIMELESS Gene

    Size:
    1208 amino acids
    Molecular mass:
    138658 Da
    Quaternary structure:
    • Homodimer or homomultimer (By similarity). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSKN1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with PER2; the interaction with PER2 is via its second PAS domain. Interacts directly with PER1 and PER3 (By similarity). Interacts with CRY2, CHEK1, ATR and ATRIP (PubMed:15798197). Interacts with CRY1 (By similarity). Interacts with CLSPN (PubMed:17141802). Interacts with TIPIN (PubMed:17116885, PubMed:17102137, PubMed:17296725). Interacts with DDX11; this interaction increases recruitment of both proteins onto chromatin in response to replication stress induction by hydroxyurea (PubMed:20124417).
    SequenceCaution:
    • Sequence=AAH39842.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TIMELESS Gene

    Alternative splice isoforms for TIMELESS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TIMELESS Gene

Post-translational modifications for TIMELESS Gene

  • Ubiquitination at posLast=288288 and isoforms=2299

Other Protein References for TIMELESS Gene

No data available for DME Specific Peptides for TIMELESS Gene

Domains & Families for TIMELESS Gene

Gene Families for TIMELESS Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for TIMELESS Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for TIMELESS Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9UNS1

UniProtKB/Swiss-Prot:

TIM_HUMAN :
  • Belongs to the timeless family.
Family:
  • Belongs to the timeless family.
genes like me logo Genes that share domains with TIMELESS: view

Function for TIMELESS Gene

Molecular function for TIMELESS Gene

UniProtKB/Swiss-Prot Function:
Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication and in the regulation of the circadian clock. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCK NPAS2-ARTNL/BMAL1 ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Forms a complex with TIPIN and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. Timeless promotes TIPIN nuclear localization. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules.
UniProtKB/Swiss-Prot Induction:
Regulated by the cell cycle. High levels in S, G(2) and M phases, with highest level in S phase. Low expression in G(0) and G(1) phases.

Phenotypes From GWAS Catalog for TIMELESS Gene

Gene Ontology (GO) - Molecular Function for TIMELESS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15798197
GO:0042803 protein homodimerization activity IEA --
GO:0046982 protein heterodimerization activity IEA --
genes like me logo Genes that share ontologies with TIMELESS: view
genes like me logo Genes that share phenotypes with TIMELESS: view

Animal Models for TIMELESS Gene

MGI Knock Outs for TIMELESS:

miRNA for TIMELESS Gene

miRTarBase miRNAs that target TIMELESS

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TIMELESS Gene

Localization for TIMELESS Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIMELESS Gene

Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TIMELESS gene
Compartment Confidence
nucleus 5
cytoskeleton 2
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TIMELESS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 17102137
GO:0005634 nucleus IDA 17102137
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with TIMELESS: view

Pathways & Interactions for TIMELESS Gene

genes like me logo Genes that share pathways with TIMELESS: view

Gene Ontology (GO) - Biological Process for TIMELESS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0002009 morphogenesis of an epithelium ISS --
GO:0006260 DNA replication TAS --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with TIMELESS: view

No data available for SIGNOR curated interactions for TIMELESS Gene

Drugs & Compounds for TIMELESS Gene

No Compound Related Data Available

Transcripts for TIMELESS Gene

Unigene Clusters for TIMELESS Gene

Timeless circadian clock:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for TIMELESS Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17a · 17b · 17c · 17d ^ 18a ·
SP1:
SP2:
SP3: - -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

ExUns: 18b ^ 19a · 19b ^ 20a · 20b ^ 21 ^ 22a · 22b ^ 23 ^ 24a · 24b ^ 25a · 25b ^ 26 ^ 27a · 27b · 27c ^ 28 ^ 29
SP1:
SP2: - - -
SP3: - -
SP4: - -
SP5:
SP6:
SP7:
SP8:
SP9:
SP10: -
SP11:
SP12:
SP13:

Relevant External Links for TIMELESS Gene

GeneLoc Exon Structure for
TIMELESS
ECgene alternative splicing isoforms for
TIMELESS

Expression for TIMELESS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TIMELESS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TIMELESS Gene

This gene is overexpressed in Plasma (32.4), Bone marrow mesenchymal stem cell (22.1), and Fetal ovary (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for TIMELESS Gene



NURSA nuclear receptor signaling pathways regulating expression of TIMELESS Gene:

TIMELESS

SOURCE GeneReport for Unigene cluster for TIMELESS Gene:

Hs.118631

mRNA Expression by UniProt/SwissProt for TIMELESS Gene:

Q9UNS1-TIM_HUMAN
Tissue specificity: Expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus and testis. Highest levels of expression in placenta, pancreas, thymus and testis.

Evidence on tissue expression from TISSUES for TIMELESS Gene

  • Nervous system(3.1)
  • Eye(2.1)
genes like me logo Genes that share expression patterns with TIMELESS: view

Primer Products

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for TIMELESS Gene

Orthologs for TIMELESS Gene

This gene was present in the common ancestor of animals.

Orthologs for TIMELESS Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TIMELESS 33 34
  • 99.64 (n)
dog
(Canis familiaris)
Mammalia TIMELESS 33 34
  • 87.39 (n)
cow
(Bos Taurus)
Mammalia TIMELESS 33 34
  • 87.16 (n)
mouse
(Mus musculus)
Mammalia Timeless 33 16 34
  • 82.61 (n)
rat
(Rattus norvegicus)
Mammalia Timeless 33
  • 82.43 (n)
oppossum
(Monodelphis domestica)
Mammalia TIMELESS 34
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TIMELESS 34
  • 73 (a)
OneToOne
chicken
(Gallus gallus)
Aves -- 34
  • 64 (a)
OneToMany
-- 34
  • 23 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia TIMELESS 34
  • 64 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia timeless 33
  • 66.27 (n)
Str.20461 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.29613 33
zebrafish
(Danio rerio)
Actinopterygii timeless 33 34
  • 63.71 (n)
fruit fly
(Drosophila melanogaster)
Insecta timeout 35 33 34
  • 47.47 (n)
tim 34
  • 14 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010787 33
  • 45.81 (n)
worm
(Caenorhabditis elegans)
Secernentea Y75B8A.22 35
  • 28 (a)
tim-1 34
  • 21 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3465 34
  • 42 (a)
OneToOne
Species where no ortholog for TIMELESS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TIMELESS Gene

ENSEMBL:
Gene Tree for TIMELESS (if available)
TreeFam:
Gene Tree for TIMELESS (if available)

Paralogs for TIMELESS Gene

(1) SIMAP similar genes for TIMELESS Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with TIMELESS: view

No data available for Paralogs for TIMELESS Gene

Variants for TIMELESS Gene

Sequence variations from dbSNP and Humsavar for TIMELESS Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs111463603 benign, uncertain-significance, Cataract 56,450,042(-) AAAAAAAAAAA/AAAAAAAAAAAA/AAAAAAAAAAAAA upstream_transcript_variant
rs137926387 likely-benign, Cataract 56,450,789(-) T/G upstream_transcript_variant
rs140453442 likely-benign, Cataract 56,450,481(-) T/C upstream_transcript_variant
rs148601602 likely-benign, Cataract 56,450,996(-) A/G upstream_transcript_variant
rs150155933 likely-benign, Cataract 56,450,606(-) C/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for TIMELESS Gene

Variant ID Type Subtype PubMed ID
esv2745927 CNV deletion 23290073
esv3549252 CNV deletion 23714750
nsv482992 CNV gain+loss 15286789

Variation tolerance for TIMELESS Gene

Residual Variation Intolerance Score: 19.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 21.74; 99.33% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIMELESS Gene

Human Gene Mutation Database (HGMD)
TIMELESS
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIMELESS

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TIMELESS Gene

Disorders for TIMELESS Gene

MalaCards: The human disease database

(4) MalaCards diseases for TIMELESS Gene - From: HGMD, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
vestibular nystagmus
  • nystagmus associated with disorder of the vestibular system
warsaw breakage syndrome
  • wabs
advanced sleep phase syndrome
  • familial advanced sleep-phase syndrome
breast cancer
  • breast cancer, familial
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TIMELESS

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TIMELESS: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIMELESS Gene

Publications for TIMELESS Gene

  1. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. (PMID: 20072116) Soria V … Urretavizcaya M (Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2010) 3 22 44 58
  2. Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint. (PMID: 17102137) Yoshizawa-Sugata N … Masai H (The Journal of biological chemistry 2007) 3 4 22 58
  3. Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. (PMID: 9856465) Sangoram AM … Takahashi JS (Neuron 1998) 2 3 4 58
  4. Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock. (PMID: 23418588) Engelen E … Tamanini F (PloS one 2013) 3 4 58
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 44 58

Products for TIMELESS Gene

Sources for TIMELESS Gene

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