InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Timeless

Summary

InnateDB Protein

IDBP-271290.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Timeless

Protein Name

timeless homolog (Drosophila)

Synonyms

C77407; Debt69; tim;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000100879

InnateDB Gene

IDBG-196902 (Timeless)

Protein Structure

UniProt Annotation

Function

Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication and in the regulation of the circadian clock. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCKNPAS2-ARTNL/BMAL1ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Forms a complex with TIPIN and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. Timeless 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. {ECO:0000269PubMed:10428031, ECO:0000269PubMed:10963667, ECO:0000269PubMed:12875843, ECO:0000269PubMed:23418588, ECO:0000269PubMed:9856465}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:10231394, ECO:0000269PubMed:10428031, ECO:0000269PubMed:23418588, ECO:0000269PubMed:24489120}.

Disease Associations

Tissue Specificity

Predominantly and robustly expressed in proliferative organs (spleen, thymus, intestine and testis) compared to those more differentiated such as kidney and liver (at protein level). Expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus and testis. Strongly expressed in the suprachiasmatic nucleus (SCN) and pars tuberalis, moderately in the cingulate cortex, pyrimidal cell layer of the piriform cortex, periventricular part of the caudate putamen, and granular layer of the cerebellum, and weakly in the cerebral cortex, gyrus dentatus, hippocampus and thalamic nuclei. In embryonic kidney, expression is highest in regions of active ureteric bud cell branching. {ECO:0000269PubMed:10231394, ECO:0000269PubMed:10428031, ECO:0000269PubMed:10963667, ECO:0000269PubMed:23418588, ECO:0000269PubMed:9856465, ECO:0000269PubMed:9856466, ECO:0000269PubMed:9891984}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 14 interaction(s) predicted by orthology.

Experimentally validated
Total	19 [view]
Protein-Protein	19 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	14 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0002009	morphogenesis of an epithelium
GO:0006351	transcription, DNA-templated
GO:0006974	cellular response to DNA damage stimulus
GO:0007067	mitotic nuclear division
GO:0007623	circadian rhythm
GO:0030324	lung development
GO:0044770	cell cycle phase transition
GO:0045892	negative regulation of transcription, DNA-templated
GO:0048754	branching morphogenesis of an epithelial tube