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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
General
nuclear protein
phosphoprotein
Properties
SIZE: entity length = 1208 aa
MW = 139 kD
COMPARTMENT: cell nucleus
MOTIF: glutamate-rich region {661-688}
MOTIF: glutamate residue (SEVERAL)
Thr phosphorylation site {T1089}
Ser phosphorylation site {S1149}
Ser phosphorylation site {S1173}
Database Correlations
OMIM 603887
UniProt Q9UNS1
PFAM correlations
Entrez Gene 8914
Kegg hsa:8914
References
- UniProt :accession Q9UNS1
- NIEHS-SNPs
http://egp.gs.washington.edu/data/timeless/
Component-of
circadian clock oscillator