TIMELESS Antibody, FITC conjugated
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Product Specs
Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Typically, we can ship your order within 1-3 business days of receiving it. Delivery times may vary depending on the shipping method and destination. For specific delivery time estimates, please consult your local distributors.
Synonyms
FLJ12640 antibody; FLJ20714 antibody; hTIM antibody; Protein timeless homolog antibody; TIM antibody; TIM_HUMAN antibody; TIM1 antibody; Timeless antibody; timeless circadian clock 1 antibody; timeless circadian clock antibody; timeless homolog antibody; TIMELESS1 antibody; Tof1 homolog antibody
Target Names
TIMELESS
Uniprot No.
Target Background
Function
The TIMELESS protein plays a crucial role in regulating various cellular processes, including DNA replication, replication fork stability, genome stability, DNA repair, and the circadian clock. It forms a complex with TIPIN, stabilizing replication forks during DNA replication. This complex regulates DNA replication processes under both normal and stressful conditions, ensuring replication fork stability and influencing CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. TIMELESS also facilitates TIPIN's nuclear localization.
TIMELESS contributes to cell survival following DNA damage or replication stress by promoting DNA repair. It accumulates at DNA damage sites in response to double-strand breaks (DSBs) and facilitates homologous recombination repair through its interaction with PARP1. It may be specifically required for the ATR-CHEK1 pathway in the replication checkpoint triggered by hydroxyurea or ultraviolet light.
TIMELESS is involved in determining the length of the circadian cycle and influencing the DNA damage-dependent phase advancing of the circadian clock. It negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1, potentially by relocating PER1 into the nucleus. Additionally, TIMELESS may play a significant role in epithelial cell morphogenesis and the formation of branching tubules.
TIMELESS contributes to cell survival following DNA damage or replication stress by promoting DNA repair. It accumulates at DNA damage sites in response to double-strand breaks (DSBs) and facilitates homologous recombination repair through its interaction with PARP1. It may be specifically required for the ATR-CHEK1 pathway in the replication checkpoint triggered by hydroxyurea or ultraviolet light.
TIMELESS is involved in determining the length of the circadian cycle and influencing the DNA damage-dependent phase advancing of the circadian clock. It negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1, potentially by relocating PER1 into the nucleus. Additionally, TIMELESS may play a significant role in epithelial cell morphogenesis and the formation of branching tubules.
Gene References Into Functions
- Research suggests that disruptions in TIMELESS expression can lead to the disruption of normal circadian rhythms, potentially promoting the survival of glioma cells and contributing to carcinogenesis. PMID: 30249891
- The TIM rs2291738 variant has been associated with chronotype dimensions. PMID: 28708003
- Inhibition of MYC significantly blocked the effects of TIMELESS on cancer stem cell (CSC) population, cell invasion, and anchor-independent cell growth. This suggests that TIMELESS plays a key role in promoting breast cancer progression and could be a potential therapeutic target. PMID: 28464854
- Stable ectopic overexpression of TIMELESS in nasopharyngeal carcinoma cell lines conferred resistance to cisplatin-induced apoptosis in vitro and in vivo, promoted an epithelial-to-mesenchymal transition phenotype, and activated the Wnt/beta-catenin pathway and downstream gene transcription. PMID: 28583847
- A crystal structure of a large N-terminal segment of human TIMELESS, spanning amino acids 1-463, has been determined at a resolution of 1.85 angstroms. This region of human TIMELESS contains a partial binding site for Tipin. PMID: 28334766
- Research provides the first evidence that TIMELESS is essential for the proper chromatin association of the CMG complex, allowing efficient DNA replication. PMID: 27587400
- Studies indicate that overexpression of TIMELESS correlates with pelvic lymph node metastasis, lymphovascular space involvement, and unfavorable overall survival (OS) and disease-free survival (DFS) in human cervical cancer. Therefore, TIMELESS expression may serve as a potential prognostic biomarker for cervical cancer patients. PMID: 27909716
- TIMELESS mutants have been identified that are unable to bind PARP1. Silencing of TIMELESS significantly impairs DNA double-strand break repair. PMID: 26456830
- The crystal structure of the TIMELESS-PARP-1 complex has been determined, providing evidence that TIMELESS is recruited to sites of DNA damage through PARP-1 to mediate homologous recombination repair of DNA double-strand breaks. PMID: 26344098
- Overexpression of TIMELESS exerts oncogenic function in human hepatocellular carcinomas (HCCs), mediated via CHEK2 and EEF1A2. PMID: 25405317
- TIMELESS and RORA genes may contribute to susceptibility to bipolar disorders and impact circadian phenotypes. PMID: 24716566
- Research suggests that the TIMELESS gene may be associated with the prophylactic response to lithium treatment in bipolar illness. PMID: 24636202
- 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. PMID: 24161199
- RNAi-mediated knockdown of TIMELESS (TIM) in NIH3T3 and U2OS cells shortens the period of the circadian cycle by 1 hour and diminishes DNA damage-dependent phase advancing. PMID: 23418588
- TIMELESS has a distinct contribution to the suppression of chromosomal instability that is independent of its heterodimeric partner, TIPIN. PMID: 23255133
- The Tim-Tipin complex (or Tim alone) can associate with DNA polymerase epsilon bound to a 40-/80-mer DNA ligand. PMID: 23511638
- All lung cancer specimens examined were positive for TIMELESS expression, while no matched normal lung tissues exhibited expression. PMID: 23173913
- The maintenance of Kaposi's Sarcoma-associated herpesvirus episomes requires TIMELESS-assisted replication fork protection at the viral terminal repeats. PMID: 23325691
- A significant association was observed between stage II, III, and IV breast cancers and TIMELESS promoter hypomethylation in peripheral blood lymphocytes in a study of 80 breast cancer cases and 80 age-matched controls. PMID: 22006848
- TIMELESS functions together with TRF1 to prevent fork collapse at telomere repeat DNA, ensuring stable maintenance of telomere length and integrity. PMID: 22672906
- TIMELESS has a function in squamous cell carcinoma (SCC) that is independent of the Tim-Tipin complex, even though the abundance of TIMELESS is reduced when Tipin is targeted for depletion. PMID: 21508667
- TIMELESS coordinates mitotic kinase activation with the termination of DNA replication. PMID: 21573113
- Findings demonstrate that TIMELESS is essential for sustaining the episomal forms of Epstein-Barr virus (EBV) DNA in latently infected cells. PMID: 21490103
- The interaction between dPERIOD and dCLOCK is TIMELESS-dependent and modulated by light, revealing a novel and unanticipated in vivo role for TIMELESS in circadian transcription. PMID: 20980603
- Data show a significant association between TIMELESS variants and depression with fatigue in females, and association to depression with early morning awakening in males. PMID: 20174623
- Research suggests that the TIMELESS-Tipin complex functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks. PMID: 20124417
- TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control. PMID: 19996108
- Down-regulation of TIMELESS in human cells significantly compromises replication and intra-S checkpoints, highlighting a close connection between the circadian cycle and the DNA damage checkpoints, partially mediated by the TIMELESS protein. PMID: 15798197
- Tipin is a checkpoint mediator that collaborates with Tim and may regulate the nuclear relocation of Claspin in response to the replication checkpoint. PMID: 17102137
- Observations explain the similar checkpoint phenotypes observed in both Tipin- and TIMELESS-depleted cells. PMID: 17116885
- TIMELESS and Tipin are functional orthologs of their replisome-associated yeast counterparts, capable of coordinating replication with genotoxic stress responses, differentiating mammalian TIMELESS from its circadian-specific paralogs. PMID: 17141802
- Findings indicate that the TIMELESS-Tipin complex mediates the UV-induced intra-S checkpoint, TIMELESS is required for maintaining DNA replication fork movement, and Tipin interacts with RPA on DNA. PMID: 17296725
- HRPAP20 and TIMELESS have been identified as promising markers of tamoxifen resistance in women with ER alpha-positive breast tumors. PMID: 17909269
Database Links
Protein Families
Timeless family
Subcellular Location
Nucleus. Chromosome.
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.
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