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    TIMELESS timeless circadian clock [ Homo sapiens (human) ]

    Gene ID: 8914, updated on 14-May-2013
    Official Symbol
    TIMELESSprovided by HGNC
    Official Full Name
    timeless circadian clockprovided by HGNC
    Primary source
    HGNC:11813
    See related
    Ensembl:ENSG00000111602; HPRD:04864; MIM:603887; Vega:OTTHUMG00000170600
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TIM; TIM1; hTIM
    Location :
    12q13.3
    Sequence :
    Chromosome: 12; NC_000012.11 (56810157..56843200, complement)
    See TIMELESS in Epigenomics, MapViewer

    Chromosome 12 - NC_000012.11Genomic Context describing neighboring genes Neighboring gene apolipoprotein F pseudogene Neighboring gene TBCC domain containing 1 pseudogene Neighboring gene major intrinsic protein of lens fiber Neighboring gene SPRY domain containing 4 Neighboring gene glutaminase 2 (liver, mitochondrial)

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Timeless-dependent DNA replication-coupled recombination promotes Kaposi's Sarcoma-associated herpesvirus episome maintenance and terminal repeat stability. Dheekollu J, et al. J Virol, 2013 Apr. PMID 23325691.
    2. Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Povlsen LK, et al. Nat Cell Biol, 2012 Oct. PMID 23000965.
    3. A census of human soluble protein complexes. Havugimana PC, et al. Cell, 2012 Aug 31. PMID 22939629.
    4. A high-throughput approach for measuring temporal changes in the interactome. Kristensen AR, et al. Nat Methods, 2012 Sep. PMID 22863883.
    5. Timeless preserves telomere length by promoting efficient DNA replication through human telomeres. Leman AR, et al. Cell Cycle, 2012 Jun 15. PMID 22672906.

    See all (59) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Kaposi's Sarcoma-associated herpesvirus episome maintenance requires Tim-assisted replication fork protection at the viral terminal repeats.
      Title: Timeless-dependent DNA replication-coupled recombination promotes Kaposi's Sarcoma-associated herpesvirus episome maintenance and terminal repeat stability.
    2. observed a significant association between stage II, III, and IV breast cancers and TIMELESS promoter hypomethylation in peripheral blood lymphocytes in 80 breast cancer cases and 80 age-matched controls
      Title: Genetic and epigenetic associations of circadian gene TIMELESS and breast cancer risk.
    3. Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity.
      Title: Timeless preserves telomere length by promoting efficient DNA replication through human telomeres.
    4. Timeless has a function in SCC that is independent of the Tim-Tipin complex, even though the abundance of Timeless is reduced when Tipin is targeted for depletion.
      Title: Timeless functions independently of the Tim-Tipin complex to promote sister chromatid cohesion in normal human fibroblasts.
    5. Tim coordinates mitotic kinase activation with termination of DNA replication.
      Title: Timeless links replication termination to mitotic kinase activation.
    6. These findings demonstrate that Tim is essential for sustaining the episomal forms of EBV DNA in latently infected cells.
      Title: The replisome pausing factor Timeless is required for episomal maintenance of latent Epstein-Barr virus.
    7. the interaction between dPERIOD and dCLOCK is TIM-dependent and modulated by light, revealing a novel and unanticipated in vivo role for TIM in circadian transcription
      Title: Two distinct modes of PERIOD recruitment onto dCLOCK reveal a novel role for TIMELESS in circadian transcription.
    8. Data show significant association between TIMELESS variants and depression with fatigue in females, and association to depression with early morning awakening in males.
      Title: Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
    9. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    Submit: New GeneRIF Correction See all (20)

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    Q9UNS1 Q16526 CRY1    HPRD  PubMed  
    Q9UNS1 O15534 PER1    HPRD  PubMed  
    Q9UNS1 O15055 PER2    HPRD  PubMed  
    Q9UNS1 TIMELESS interacting protein TIPIN    HPRD  PubMed  
    BioGRID:114428 BioGRID:313463 ATRIP    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114428 BioGRID:107536 CHEK1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114428 BioGRID:122015 CLSPN    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114428 BioGRID:107798 CRY2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114428 BioGRID:198756 Clock    BioGRID  PubMed Phenotypic Suppression 
    BioGRID:114428 BioGRID:108577 FKBP3    BioGRID  PubMed Co-fractionation 
    BioGRID:114428 BioGRID:111125 PCBD1    BioGRID  PubMed Two-hybrid 
    BioGRID:114428 BioGRID:111142 PCNA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114428 BioGRID:202111 Per1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114428 BioGRID:202112 Per2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114428 BioGRID:112550 SP1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114428 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114428 BioGRID:112876 TF    BioGRID  PubMed Two-hybrid 
    BioGRID:114428 BioGRID:120300 TIPIN    BioGRID  PubMed Affinity Capture-Western; Co-purification 
    BioGRID:114428 BioGRID:122325 TUT1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114428 BioGRID:204198 Timeless    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114428 BioGRID:211238 Tipin    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114428 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114428 BioGRID:113349 XRCC1    BioGRID  PubMed Co-fractionation 
    BioGRID:114428 BioGRID:129825 ZSCAN1    BioGRID  PubMed Two-hybrid 
    BioGRID:114428 BioGRID:57782 per    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 

    Markers

    Genotypes

    Homology

    Clone Names

    • FLJ12640, FLJ20714

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein heterodimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein homodimerization activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    branching morphogenesis of an epithelial tube IEA
    Inferred from Electronic Annotation
    more info
    		  
    cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    circadian rhythm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    detection of abiotic stimulus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    embryo development IEA
    Inferred from Electronic Annotation
    more info
    		  
    lung development IEA
    Inferred from Electronic Annotation
    more info
    		  
    mitosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    morphogenesis of an epithelium ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of transcription from RNA polymerase II promoter IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of transcription, DNA-dependent IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    regulation of S phase IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    NOT regulation of cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    response to DNA damage stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to abiotic stimulus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    transcription, DNA-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    nuclear chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IC
    Inferred by Curator
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Preferred Names
    protein timeless homolog
    Names
    protein timeless homolog
    Tof1 homolog
    timeless homolog
    timeless circadian clock 1

    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)

    1. NM_003920.3 → NP_003911.2  protein timeless homolog

      Status: VALIDATED

      Source sequence(s)
      AF098162, AK000721, BC031514, BE503292, BP363571
      Consensus CDS
      CCDS8918.1
      UniProtKB/Swiss-Prot
      Q9UNS1
      Related
      ENSP00000450607, OTTHUMP00000244115, ENST00000553532, OTTHUMT00000409771
      Conserved Domains (2) summary
      pfam04821
      Location:21 – 285
      Blast Score: 872
      TIMELESS; Timeless protein
      pfam05029
      Location:728 – 1200
      Blast Score: 1088
      TIMELESS_C; Timeless protein C terminal region

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000012.11 Reference GRCh37.p10 Primary Assembly

      Range
      56810157..56843200, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000144.1 Alternate HuRef

      Range
      53849203..53882241, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018923.1 Alternate CHM1_1.0

      Range
      56644291..56677346, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01008424.1 (58023..91061) None
    genomic AC024884.31 (17868..50127) None
    genomic AMYH01004504.1 (135846..139487) None
    genomic AMYH01004505.1 None
    genomic CH471054.1 EAW96939.1
    genomic EU627094.1 ACD11488.1
    mRNA AB015597.1 BAA36499.1
    mRNA AF098162.1 AAC80011.1
    mRNA AK000721.1 None
    mRNA AK022702.1 BAG51106.1
    mRNA AK296869.1 BAG59432.1
    mRNA AY207390.1 None
    mRNA BC031514.1 None
    mRNA BC039842.1 AAH39842.1
    mRNA BC050557.1 AAH50557.1
    mRNA BE503292.1 None
    mRNA BP363571.1 None
    mRNA BX640990.1 CAE45996.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UNS1.2 GenPept UniProtKB/Swiss-Prot:Q9UNS1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

      • Order cDNA clone
        Order cDNA clone
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      • BioSystems
        BioSystems
      • Books
        Links between Entrez Gene and 'Books' are established if a GeneID is explicitly referenced in a book.
      • CCDS
        Links from Gene to CCDS are established if a gene encodes a protein sequence that is a member of a Consensus CDS (CCDS).
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
      • EST
        Link to related EST entry
      • Full text in PMC
        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • Genome
        Genome records having the gene annotated on corresponding genomic reference sequence.
      • GEO Profiles
        Related GEO
      • HomoloGene
        Links between HomoloGene and Gene are provided by the HomoloGene group when a gene is included in a HomoloGene record.
      • Map Viewer
        These links are maintained by the Map Viewer group and are provided when a GeneID is annotated on a map for the same species.
      • Nucleotide
        Link to related Nucleotide entry
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        Related Probe entry
      • Protein
        Link to related protein entry
      • PubChem Compound
        PubChem Compounds
      • PubChem Substance
        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • SNP
        Related SNP records
      • SNP: GeneView
        SNPs linked from GeneView
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        Gene Genotype Report
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

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