TIMELESS Positive Control

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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

TIMELESS: 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. Belongs to the timeless family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Transcription, coactivator/corepressor

Cellular Component: microtubule cytoskeleton; nuclear chromatin; nucleolus; nucleus

Molecular Function: protein binding; protein heterodimerization activity; protein homodimerization activity

Biological Process: branching morphogenesis of a tube; cell cycle; cell division; embryonic development; kidney development; lung development; mitosis; multicellular organismal development; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; positive regulation of circadian rhythm; regulation of circadian rhythm; regulation of transcription, DNA-dependent; response to DNA damage stimulus; rhythmic process; transcription, DNA-dependent; ureteric bud branching