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TIMELESS timeless circadian regulator [ Homo sapiens (human) ]

Gene ID: 8914, updated on 2-Oct-2018

Summary

Official Symbol
TIMELESSprovided by HGNC
Official Full Name
timeless circadian regulatorprovided by HGNC
Primary source
HGNC:HGNC:11813
See related
Ensembl:ENSG00000111602 MIM:603887; Vega:OTTHUMG00000170600
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TIM; TIM1; hTIM
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. [provided by RefSeq, Feb 2014]
Expression
Ubiquitous expression in lymph node (RPKM 8.6), bone marrow (RPKM 8.5) and 25 other tissues See more
Orthologs

Genomic context

See TIMELESS in Genome Data Viewer
Location:
12q13.3
Exon count:
29
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 12 NC_000012.12 (56416373..56449465, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (56810157..56843200, complement)

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

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
NHGRI GWA Catalog
Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
NHGRI GWA Catalog

Pathways from BioSystems

  • Circadian rhythm pathway, organism-specific biosystem (from Pathway Interaction Database)
    Circadian rhythm pathway, organism-specific biosystem
    Circadian rhythm pathway
  • Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
    Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
  • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
    DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
    HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) of replication-independent DNA double strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM fol...
  • Homology Directed Repair, organism-specific biosystem (from REACTOME)
    Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
  • Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
    Processing of DNA double-strand break ends, organism-specific biosystemHomology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ci...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ12640, FLJ20714

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
DNA repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA replication checkpoint IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
branching morphogenesis of an epithelial tube IEA
Inferred from Electronic Annotation
more info
 
cell cycle phase transition IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell division IEA
Inferred from Electronic Annotation
more info
 
cellular response to DNA damage stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to DNA damage stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to bleomycin IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to cisplatin IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to hydroxyurea IMP
Inferred from Mutant Phenotype
more info
PubMed 
circadian rhythm ISS
Inferred from Sequence or Structural Similarity
more info
 
detection of abiotic stimulus TAS
Traceable Author Statement
more info
PubMed 
lung development IEA
Inferred from Electronic Annotation
more info
 
morphogenesis of an epithelium ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of double-strand break repair IMP
Inferred from Mutant Phenotype
more info
PubMed 
NOT regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of circadian rhythm IMP
Inferred from Mutant Phenotype
more info
PubMed 
replication fork arrest IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
replication fork protection IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
nuclear chromatin IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nuclear chromatin IDA
Inferred from Direct Assay
more info
PubMed 
nuclear chromosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IC
Inferred by Curator
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
replication fork protection complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

Preferred Names
protein timeless homolog
Names
Tof1 homolog
timeless circadian clock 1
timeless homolog

NCBI Reference Sequences (RefSeq)

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_001330295.1NP_001317224.1  protein timeless homolog isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The encoded isoform (2) has the same N- and C-termini, but is one amino acid shorter than isoform 1.
    Source sequence(s)
    AF098162, AK000721, BC031514, BC039842, BE503292, HY040179
    Consensus CDS
    CCDS81699.1
    UniProtKB/Swiss-Prot
    Q9UNS1
    Related
    ENSP00000229201.4, ENST00000229201.4
    Conserved Domains (2) summary
    pfam05029
    Location:7271199
    TIMELESS_C; Timeless protein C terminal region
    pfam04821
    Location:25283
    TIMELESS; Timeless protein
  2. NM_003920.4NP_003911.2  protein timeless homolog isoform 1

    See identical proteins and their annotated locations for NP_003911.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).
    Source sequence(s)
    AF098162, AK000721, BC031514, BE503292, HY040179
    Consensus CDS
    CCDS8918.1
    UniProtKB/Swiss-Prot
    Q9UNS1
    Related
    ENSP00000450607.1, OTTHUMP00000244115, ENST00000553532.5, OTTHUMT00000409771
    Conserved Domains (2) summary
    pfam05029
    Location:7281200
    TIMELESS_C; Timeless protein C terminal region
    pfam04821
    Location:25284
    TIMELESS; Timeless protein

RNA

  1. NR_138471.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF098162, AK000721, BC031514, BE503292, BX640990, HY040179

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p12 Primary Assembly

    Range
    56416373..56449465 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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