TIMELESS timeless circadian regulator [Homo sapiens (human)] - Gene

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; AllianceGenome:HGNC:11813
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; FASPS4
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: mouse all
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Genomic context

Location:: 12q13.3

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (56416363..56449426, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (56384058..56417137, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (56810147..56843210, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.
Title: SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.
ncRNAs-mediated TIMELESS overexpression in lung adenocarcinoma correlates with reduced tumor immune cell infiltration and poor prognosis.
Title: ncRNAs-mediated TIMELESS overexpression in lung adenocarcinoma correlates with reduced tumor immune cell infiltration and poor prognosis.
TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.
Title: TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.
An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker.
Title: An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker.
TIMELESS promotes the proliferation and migration of lung adenocarcinoma cells by activating EGFR through AMPK and SPHK1 regulation.
Title: TIMELESS promotes the proliferation and migration of lung adenocarcinoma cells by activating EGFR through AMPK and SPHK1 regulation.
Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.
Title: Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.
TIMELESS upregulates PD-L1 expression and exerts an immunosuppressive role in breast cancer.
Title: TIMELESS upregulates PD-L1 expression and exerts an immunosuppressive role in breast cancer.
Regulation of mineralocorticoid receptor activation by circadian protein TIMELESS.
Title: Regulation of mineralocorticoid receptor activation by circadian protein TIMELESS.
Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism.
Title: Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism.
MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS.
Title: MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS.

Submit: New GeneRIF Correction See all GeneRIFs (59)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Advance sleep phase syndrome, familial, 4 MedGen: C5774204 OMIM: 620015 GeneReviews: Not available	not available

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TIMELESS_1103 (e-PCR)
- UniSTS:277815

RH48818 (e-PCR)
- UniSTS:51082

D12S1778 (e-PCR)
- UniSTS:8604

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
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	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 replication checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in branching morphogenesis of an epithelial tube	IEA Inferred from Electronic Annotation more info
involved_in cell cycle phase transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in cellular response to bleomycin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to cisplatin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to hydroxyurea	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of abiotic stimulus	TAS Traceable Author Statement more info	PubMed
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in morphogenesis of an epithelium	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in replication fork arrest	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IC Inferred by Curator more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of replication fork protection complex	IBA Inferred from Biological aspect of Ancestor more info
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein timeless homolog

Names: Tof1 homolog; timeless circadian clock 1; 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_001330295.2 → NP_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)

AC024884

Consensus CDS

CCDS81699.1

UniProtKB/Swiss-Prot

Q9UNS1

Related

ENSP00000229201.4, ENST00000229201.4

Conserved Domains (2) summary

pfam05029
Location:727 → 1199

TIMELESS_C; Timeless protein C terminal region

pfam04821
Location:25 → 283

TIMELESS; Timeless protein
NM_003920.5 → NP_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)

AC024884

Consensus CDS

CCDS8918.1

UniProtKB/Swiss-Prot

B2ZAV0, O94802, Q86VM1, Q8IWH3, Q9UNS1

Related

ENSP00000450607.1, ENST00000553532.6

Conserved Domains (2) summary

pfam04821
Location:25 → 284

TIMELESS; Timeless protein

pfam05029
Location:1006 → 1092

TIMELESS_C; Timeless protein C terminal region

RNA

NR_138471.2 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)

AC024884