timeless homolog; hTIM (TIMELESS TIM TIM1 TIMELESS1)

Function

• required for normal progression of S-phase
• role in 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
• role in cell survival after DNA damage or DNA replication stress
• may be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light
• may have role in epithelial morphogenesis & in formation of branching tubules
• component of the circadian core oscillator,
  • interacts directly with PER1, PER2 & PER3
    • interacts with PER2 via its second PAS domain in vitro
• binds CRY1, CRY2, CHEK1, ATR & ATRIP (putative)
• interacts with TIPIN & CLSPN

Structure

• homomultimer
• belongs to the timeless family

Compartment

nucleus

Alternative splicing

named isoforms=2

Expression

• expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus & testis
• highest levels of expression in placenta, pancreas, thymus & testis
• expression is regulated by the cell cycle
  • high levels in S phase, G2 phase & M phase
  • highest level in S phase
• low expression in G0 phase & G1 phase

More general terms

• nuclear protein
• phosphoprotein

Component of

• circadian core oscillator

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8914
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8914
• OMIM: https://mirror.omim.org/entry/603887
• UniProt: http://www.uniprot.org/uniprot/Q9UNS1.html