Human Gene TIMELESS (uc001slf.2)
  Description: Homo sapiens timeless circadian clock (TIMELESS), mRNA.
RefSeq Summary (NM_003920): 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].
Transcript (Including UTRs)
   Position: hg19 chr12:56,810,157-56,843,200 Size: 33,044 Total Exon Count: 29 Strand: -
Coding Region
   Position: hg19 chr12:56,811,500-56,827,954 Size: 16,455 Coding Exon Count: 28 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:56,810,157-56,843,200)mRNA (may differ from genome)Protein (1208 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TIM_HUMAN
DESCRIPTION: RecName: Full=Protein timeless homolog; Short=hTIM;
FUNCTION: Required for normal progression of S-phase. Involved in the circadian rhythm autoregulatory loop. Negatively regulates CLOCK-NPAS2/BMAL1-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. 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.
SUBUNIT: Homomultimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSKN1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with PER1, PER2 and PER3. Interacts with PER2 via its second PAS domain in vitro. Binds CRY1, CRY2, CHEK1, ATR and ATRIP (By similarity). Interacts with TIPIN and CLSPN.
INTERACTION: O14757:CHEK1; NbExp=2; IntAct=EBI-2212315, EBI-974488;
SUBCELLULAR LOCATION: Nucleus.
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.
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.
SIMILARITY: Belongs to the timeless family.
SEQUENCE CAUTION: Sequence=AAH39842.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/timeless/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TIMELESS
CDC HuGE Published Literature: TIMELESS
Positive Disease Associations: asthma; atopy , rheumatoid arthritis
Related Studies:
  1. asthma; atopy
    Chae, S. C. et al. 2003, The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population., Biochemical and biophysical research communications. 2003 Dec;312(2):346-50. [PubMed 14637143]
    Our results strongly suggest that the 5383+AF8-5397del variation site of Tim-1 exon 4 might be associated with atopic dermatitis susceptibility.
  2. rheumatoid arthritis
    Chae, S. C. et al. 2004, The exon 4 variations of Tim-1 gene are associated with rheumatoid arthritis in a Korean population., Biochemical and biophysical research communications. 2004 Mar;315(4):971-5. [PubMed 14985107]
    Our results strongly suggest that the variations of Tim-1 exon 4 might be associated with the susceptibility to RA.
  3. rheumatoid arthritis
    Chae, S. C. et al. 2004, The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population., Immunogenetics. 2005 Jan;56(10):696-701. [PubMed 15565336]
    Our results strongly suggest that polymorphism in the Tim-1 promoter region might be associated with susceptibility to RA.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TIMELESS
Diseases sorted by gene-association score: vestibular nystagmus (16), warsaw breakage syndrome (14), breast cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.97 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 185.48 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -78.70168-0.468 Picture PostScript Text
3' UTR -431.231343-0.321 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006906 - Timeless
IPR007725 - TIMELESS_C

Pfam Domains:
PF04821 - Timeless protein
PF05029 - Timeless protein C terminal region

ModBase Predicted Comparative 3D Structure on Q9UNS1
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene DetailsGene Details Gene DetailsGene DetailsGene Details
Gene SorterGene Sorter Gene SorterGene SorterGene Sorter
 RGDEnsemblFlyBaseWormBaseSGD
 Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence
 AlignmentAlignmentAlignmentAlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0002009 morphogenesis of an epithelium
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006974 cellular response to DNA damage stimulus
GO:0007049 cell cycle
GO:0007275 multicellular organism development
GO:0007623 circadian rhythm
GO:0009582 detection of abiotic stimulus
GO:0030324 lung development
GO:0042752 regulation of circadian rhythm
GO:0044770 cell cycle phase transition
GO:0045892 negative regulation of transcription, DNA-templated
GO:0048511 rhythmic process
GO:0048754 branching morphogenesis of an epithelial tube
GO:0051301 cell division
GO:0072711 cellular response to hydroxyurea
GO:0072719 cellular response to cisplatin
GO:1904976 cellular response to bleomycin
GO:2000781 positive regulation of double-strand break repair
GO:0042127 regulation of cell proliferation

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm


-  Descriptions from all associated GenBank mRNAs
  AK000721 - Homo sapiens cDNA FLJ20714 fis, clone HUV00275, highly similar to AF098162 Homo sapiens timeless homolog mRNA.
LF384696 - JP 2014500723-A/192199: Polycomb-Associated Non-Coding RNAs.
JD063471 - Sequence 44495 from Patent EP1572962.
JD275495 - Sequence 256519 from Patent EP1572962.
JD275494 - Sequence 256518 from Patent EP1572962.
JD497140 - Sequence 478164 from Patent EP1572962.
JD275493 - Sequence 256517 from Patent EP1572962.
JD497139 - Sequence 478163 from Patent EP1572962.
JD089470 - Sequence 70494 from Patent EP1572962.
BC031514 - Homo sapiens timeless homolog (Drosophila), mRNA (cDNA clone IMAGE:3874072).
AF098162 - Homo sapiens timeless homolog mRNA, complete cds.
AK022702 - Homo sapiens cDNA FLJ12640 fis, clone NT2RM4001940, highly similar to Timeless homolog.
BC050557 - Homo sapiens timeless homolog (Drosophila), mRNA (cDNA clone MGC:57696 IMAGE:5574624), complete cds.
BX640990 - Homo sapiens mRNA; cDNA DKFZp686H09231 (from clone DKFZp686H09231).
JD521159 - Sequence 502183 from Patent EP1572962.
JD527668 - Sequence 508692 from Patent EP1572962.
JD062326 - Sequence 43350 from Patent EP1572962.
JD565964 - Sequence 546988 from Patent EP1572962.
JD296591 - Sequence 277615 from Patent EP1572962.
JD184900 - Sequence 165924 from Patent EP1572962.
AK296869 - Homo sapiens cDNA FLJ58786 complete cds, highly similar to Timeless homolog.
JD419671 - Sequence 400695 from Patent EP1572962.
JD326711 - Sequence 307735 from Patent EP1572962.
JD244935 - Sequence 225959 from Patent EP1572962.
JD119227 - Sequence 100251 from Patent EP1572962.
JD113231 - Sequence 94255 from Patent EP1572962.
AB015597 - Homo sapiens hTIM1 mRNA, complete cds, similar to Droshophila timeless gene sequence.
LF324468 - JP 2014500723-A/131971: Polycomb-Associated Non-Coding RNAs.
LF324467 - JP 2014500723-A/131970: Polycomb-Associated Non-Coding RNAs.
LF324466 - JP 2014500723-A/131969: Polycomb-Associated Non-Coding RNAs.
AY207390 - Homo sapiens timeless protein TIM1-like mRNA, partial sequence.
LF324465 - JP 2014500723-A/131968: Polycomb-Associated Non-Coding RNAs.
BC039842 - Homo sapiens, Similar to timeless homolog (Drosophila), clone IMAGE:6063535, mRNA, partial cds.
LF324464 - JP 2014500723-A/131967: Polycomb-Associated Non-Coding RNAs.
LF324463 - JP 2014500723-A/131966: Polycomb-Associated Non-Coding RNAs.
LF324462 - JP 2014500723-A/131965: Polycomb-Associated Non-Coding RNAs.
LF324461 - JP 2014500723-A/131964: Polycomb-Associated Non-Coding RNAs.
JD378784 - Sequence 359808 from Patent EP1572962.
JD142582 - Sequence 123606 from Patent EP1572962.
MA620273 - JP 2018138019-A/192199: Polycomb-Associated Non-Coding RNAs.
MA560045 - JP 2018138019-A/131971: Polycomb-Associated Non-Coding RNAs.
MA560044 - JP 2018138019-A/131970: Polycomb-Associated Non-Coding RNAs.
MA560043 - JP 2018138019-A/131969: Polycomb-Associated Non-Coding RNAs.
MA560042 - JP 2018138019-A/131968: Polycomb-Associated Non-Coding RNAs.
MA560041 - JP 2018138019-A/131967: Polycomb-Associated Non-Coding RNAs.
MA560040 - JP 2018138019-A/131966: Polycomb-Associated Non-Coding RNAs.
MA560039 - JP 2018138019-A/131965: Polycomb-Associated Non-Coding RNAs.
MA560038 - JP 2018138019-A/131964: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9UNS1 (Reactome details) participates in the following event(s):

R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs
R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5693538 Homology Directed Repair
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-73894 DNA Repair

-  Other Names for This Gene
  Alternate Gene Symbols: B2ZAV0, NM_003920, NP_003911, O94802, Q86VM1, Q8IWH3, Q9UNS1, TIM, TIM1, TIMELESS1, TIM_HUMAN
UCSC ID: uc001slf.2
RefSeq Accession: NM_003920
Protein: Q9UNS1 (aka TIM_HUMAN)
CCDS: CCDS8918.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_003920.3
exon count: 29CDS single in 3' UTR: no RNA size: 5154
ORF size: 3627CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 6917.00frame shift in genome: no % Coverage: 99.69
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.