Timeless (Tim1)

Several endogenous factors have been linked to rhythmicity or circadian behavior of living organisms. In Drosophila, the genes period (dPer) and timeless (tim), and in Neurospora frequency (frq), have been proposed to be responsible for their circadian rhythm. In mammals, the suprachiasmatic nuclei (SCN) of the anterior hypothalamus serves as a master circadian clock with a measurable circadian rhythm. In drosophila, the RNA and protein products of per and tim oscillate and may be involved in rhythm regulation. The levels of per and tim is positively regulated by two basic helix-loop-helix (bHLH)/PAS proteins, dCLOCK and dBMAL1, which heterodimerize and bind to E box enhancers. Translated per and tim are phosphorylated, form heterodimers, and then translocate to nucleus. Once in the nucleus, PER and TIM function as negative regulators of their own transcription. Recently drosophila homolog of mammalian TIM have been cloned and characterized (1). Human Timeless 1 (hTIM1; 1208 aa, chromosome 12q12-13) and mouse TIM1 (1197 aa, chromosome 10D3) share 83% identity. Tim1 is weakly expressed in SCN, and in several peripheral tissues (eyes, spleen and testis). Unlike drosophila, mouse Tim1 do not oscillate in the SCN or modulated by light exposure. Human TIM1 and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of mPER1 promoter.\n\nApplications: \nSuitable for use in ELISA, Western Blot. Other applications not tested.\n\nRecommended Dilution:\nWestern Blot: 1:1000-1:5000\nELISA: 1:10,000-1:100,000 using 50-100ng of control peptide/well.\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. For long-term storage, store at -20 degrees C. Aliquots are stable for at least 12 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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