Property Summary

NCBI Gene PubMed Count 60
PubMed Score 550.71
PubTator Score 56.63

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (21)

Disease log2 FC p
glioblastoma 2.100 1.0e-05
osteosarcoma -1.192 3.4e-02
group 3 medulloblastoma 3.400 8.9e-09
atypical teratoid / rhabdoid tumor 2.400 1.4e-09
medulloblastoma, large-cell 2.700 6.4e-06
primitive neuroectodermal tumor 2.600 6.3e-06
Atopic dermatitis 1.200 2.6e-06
adrenocortical carcinoma 1.651 1.1e-04
tuberculosis 1.200 1.4e-05
non-small cell lung cancer 2.034 3.4e-28
lung cancer 3.400 5.3e-06
colon cancer 1.400 1.6e-03
pediatric high grade glioma 1.700 2.3e-06
lung adenocarcinoma 1.500 3.1e-11
nasopharyngeal carcinoma 1.200 2.9e-05
psoriasis 1.100 5.4e-13
inflammatory breast cancer 1.500 1.3e-05
breast carcinoma 1.100 1.7e-35
ductal carcinoma in situ 1.100 9.2e-04
invasive ductal carcinoma 1.500 1.4e-04
ovarian cancer 1.500 1.9e-04

 MGI Phenotype (1)

Protein-protein Interaction (4)

Gene RIF (45)

PMID Text
26456830 TIMELESS mutants unable to bind PARP1. TIMELESS silencing significantly impairs DNA double-strand break repair.
26344098 Data reports the crystal structure of Timeless-PARP-1 complex and provides evidence that Timeless is recruited to sites of DNA damage through PARP-1 to mediate homologous recombination repair of DNA double-strand breaks.
25405317 overexpression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2.
24716566 TIMELESS and RORA genes may confer susceptibility to bipolar disorders and impact on circadian phenotypes
24636202 The results of this study suggest that the TIMELESS gene may be associated with the lithium prophylactic response in bipolar illness.
24161199 TIMELESS is frequently overexpressed in various types of tumor tissues, and elevated TIMELESS expression is associated with advanced tumor stage and poorer breast cancer prognosis.
23511638 Tim-Tipin complex (or Tim alone) is able to associate with DNA polymerase epsilon bound to a 40-/80-mer DNA ligand.
23418588 Data indicate that RNAi-mediated knockdown of TIMELESS (TIM) in NIH3T3 and U2OS cells shortens the period by 1 hour and diminishes DNA damage-dependent phase advancing.
23325691 Kaposi's Sarcoma-associated herpesvirus episome maintenance requires Tim-assisted replication fork protection at the viral terminal repeats.
23255133 TIMELESS has a distinct contribution to suppression of chromosomal instability that is independent of its heterodimeric partner, TIPIN.
23173913 All lung cancer specimens but no matched normal lung tissues were positive for TIM expression.
22672906 Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity.
22006848 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
21573113 Tim coordinates mitotic kinase activation with termination of DNA replication.
21508667 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.
21490103 These findings demonstrate that Tim is essential for sustaining the episomal forms of EBV DNA in latently infected cells.
20980603 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
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20554694 Observational study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20180986 Observational study of gene-disease association. (HuGE Navigator)
20174623 Data show significant association between TIMELESS variants and depression with fatigue in females, and association to depression with early morning awakening in males.
20174623 Observational study of gene-disease association. (HuGE Navigator)
20149345 Observational study of gene-disease association. (HuGE Navigator)
20124417 The results suggest that Timeless-Tipin functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks.
20072116 Observational study of gene-disease association. (HuGE Navigator)
19996108 TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control
19934327 Observational study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19839995 Observational study of gene-disease association. (HuGE Navigator)
19693801 Observational study of gene-disease association. (HuGE Navigator)
19470168 Observational study of gene-disease association. (HuGE Navigator)
18228528 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17909269 HRPAP20 and TIMELESS as promising markers of tamoxifen resistance in women with ER alpha-positive breast tumors.
17296725 These findings indicate that the Tim-Tipin complex mediates the UV-induced intra-S checkpoint, Tim is needed to maintain DNA replication fork movement, Tipin interacts with RPA on DNA.
17141802 TIM and Tipin are functional orthologs of their replisome-associated yeast counterparts capable of coordinating replication with genotoxic stress responses, and distinguishes mammalian TIM from the circadian-specific paralogs.
17116885 observation explains the similar checkpoint phenotypes observed in both Tipin- and Timeless-depleted cells
17102137 Tipin is a checkpoint mediator that cooperates with Tim and may regulate the nuclear relocation of Claspin in response to replication checkpoint
16507006 Observational study of gene-disease association. (HuGE Navigator)
15798197 Down-regulation of Timeless in human cells seriously compromises replication and intra-S checkpoints, indicating an intimate connection between the circadian cycle and the DNA damage checkpoints that is in part mediated by the Timeless protein.
15565336 Observational study of gene-disease association. (HuGE Navigator)
15300647 Observational study of gene-disease association. (HuGE Navigator)
14985107 Observational study of gene-disease association. (HuGE Navigator)
14637143 Observational study of gene-disease association. (HuGE Navigator)
11382904 Observational study of gene-disease association. (HuGE Navigator)

AA Sequence

MDLHMMNCELLATCSALGYLEGDTYHKEPDCLESVKDLIRYLRHEDETRDVRQQLGAAQILQSDLLPILT      1 - 70
QHHQDKPLFDAVIRLMVNLTQPALLCFGNLPKEPSFRHHFLQVLTYLQAYKEAFASEKAFGVLSETLYEL     71 - 140
LQLGWEERQEEDNLLIERILLLVRNILHVPADLDQEKKIDDDASAHDQLLWAIHLSGLDDLLLFLASSSA    141 - 210
EEQWSLHVLEIVSLMFRDQNPEQLAGVGQGRLAQERSADFAELEVLRQREMAEKKTRALQRGNRHSRFGG    211 - 280
SYIVQGLKSIGERDLIFHKGLHNLRNYSSDLGKQPKKVPKRRQAARELSIQRRSALNVRLFLRDFCSEFL    281 - 350
ENCYNRLMGSVKDHLLREKAQQHDETYYMWALAFFMAFNRAASFRPGLVSETLSVRTFHFIEQNLTNYYE    351 - 420
MMLTDRKEAASWARRMHLALKAYQELLATVNEMDISPDEAVRESSRIIKNNIFYVMEYRELFLALFRKFD    421 - 490
ERCQPRSFLRDLVETTHLFLKMLERFCRSRGNLVVQNKQKKRRKKKKKVLDQAIVSGNVPSSPEEVEAVW    491 - 560
PALAEQLQCCAQNSELSMDSVVPFDAASEVPVEEQRAEAMVRIQDCLLAGQAPQALTLLRSAREVWPEGD    561 - 630
VFGSQDISPEEEIQLLKQILSAPLPRQQGPEERGAEEEEEEEEEEEEELQVVQVSEKEFNFLDYLKRFAC    631 - 700
STVVRAYVLLLRSYQQNSAHTNHCIVKMLHRLAHDLKMEALLFQLSVFCLFNRLLSDPAAGAYKELVTFA    701 - 770
KYILGKFFALAAVNQKAFVELLFWKNTAVVREMTEGYGSLDDRSSSRRAPTWSPEEEAHLRELYLANKDV    771 - 840
EGQDVVEAILAHLNTVPRTRKQIIHHLVQMGLADSVKDFQRKGTHIVLWTGDQELELQRLFEEFRDSDDV    841 - 910
LGHIMKNITAKRSRARIVDKLLALGLVAERRELYKKRQKKLASSILPNGAESLKDFCQEDLEEEENLPEE    911 - 980
DSEEEEEGGSEAEQVQGSLVLSNENLGQSLHQEGFSIPLLWLQNCLIRAADDREEDGCSQAVPLVPLTEE    981 - 1050
NEEAMENEQFQQLLRKLGVRPPASGQETFWRIPAKLSPTQLRRAAASLSQPEEEQKLQPELQPKVPGEQG   1051 - 1120
SDEEHCKEHRAQALRALLLAHKKKAGLASPEEEDAVGKEPLKAAPKKRQLLDSDEEQEEDEGRNRAPELG   1121 - 1190
APGIQKKKRYQIEDDEDD                                                       1191 - 1208
//

Text Mined References (71)

PMID Year Title
26456830 2015 TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response.
26344098 2015 Timeless Interacts with PARP-1 to Promote Homologous Recombination Repair.
25405317 2015 Protumorigenic role of Timeless in hepatocellular carcinoma.
24716566 2014 Association between circadian genes, bipolar disorders and chronotypes.
24636202 2014 Polymorphism of circadian clock genes and prophylactic lithium response.
24161199 2013 Potential cancer-related role of circadian gene TIMELESS suggested by expression profiling and in vitro analyses.
24144296 2013 Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
23797032 2013 Roles of ChlR1 DNA helicase in replication recovery from DNA damage.
23511638 2013 The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity.
23418588 2013 Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock.
23325691 2013 Timeless-dependent DNA replication-coupled recombination promotes Kaposi's Sarcoma-associated herpesvirus episome maintenance and terminal repeat stability.
23255133 2013 Separation of intra-S checkpoint protein contributions to DNA replication fork protection and genomic stability in normal human fibroblasts.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23173913 2013 TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival.
22672906 2012 Timeless preserves telomere length by promoting efficient DNA replication through human telomeres.
22610502 2012 Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
22006848 2012 Genetic and epigenetic associations of circadian gene TIMELESS and breast cancer risk.
21670590 2011 Timeless makes some time for itself.
21573113 2011 Timeless links replication termination to mitotic kinase activation.
21508667 2011 Timeless functions independently of the Tim-Tipin complex to promote sister chromatid cohesion in normal human fibroblasts.
21490103 2011 The replisome pausing factor Timeless is required for episomal maintenance of latent Epstein-Barr virus.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21269460 2011 Initial characterization of the human central proteome.
20980603 2010 Two distinct modes of PERIOD recruitment onto dCLOCK reveal a novel role for TIMELESS in circadian transcription.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20554694 Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20180986 2010 CLOCK is suggested to associate with comorbid alcohol use and depressive disorders.
20174623 2010 Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
20149345 2010 CLOCK gene variants associate with sleep duration in two independent populations.
20139726 2010 The many facets of the Tim-Tipin protein families' roles in chromosome biology.
20124417 2010 Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion.
20072116 2010 Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19996108 2010 Mammalian TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control.
19934327 2009 Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19839995 2009 Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia.
19693801 2010 PER2 variantion is associated with depression vulnerability.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19470168 2009 NPAS2 and PER2 are linked to risk factors of the metabolic syndrome.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18228528 2008 Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm.
17909269 2007 Oligonucleotide microarray analysis of estrogen receptor alpha-positive postmenopausal breast carcinomas: identification of HRPAP20 and TIMELESS as outstanding candidate markers to predict the response to tamoxifen.
17296725 2007 The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement.
17141802 2007 Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors.
17116885 2006 Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function.
17102137 2007 Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16541075 2006 The finished DNA sequence of human chromosome 12.
16507006 2006 Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia.
15946665 2005 Upregulation of human mitochondrial NADH dehydrogenase subunit 5 in intestinal epithelial cells is modulated by Vibrio cholerae pathogenesis.
15798197 2005 Coupling of human circadian and cell cycles by the timeless protein.
15565336 2005 The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15302935 2004 Large-scale characterization of HeLa cell nuclear phosphoproteins.
15300647 2004 [Exploring the possibility of a relationship between polymorphism in TIM-1 and allergic asthma in children of the Hans from Hubei province of China].
14985107 2004 The exon 4 variations of Tim-1 gene are associated with rheumatoid arthritis in a Korean population.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14637143 2003 The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population.
12875843 2003 Tipin, a novel timeless-interacting protein, is developmentally co-expressed with timeless and disrupts its self-association.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11382904 2000 A polymorphism in the human timeless gene is not associated with diurnal preferences in normal adults.
10428031 1999 mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop.
9891984 1998 Identification of the mammalian homologues of the Drosophila timeless gene, Timeless1.
9856466 1998 Molecular analysis of mammalian timeless.
9856465 1998 Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription.