InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TIMELESS

Summary

InnateDB Protein

IDBP-595680.3

Last Modified

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

Gene Symbol

TIMELESS

Protein Name

timeless homolog (Drosophila)

Synonyms

hTIM; TIM; TIM1;

Species

Homo sapiens

Ensembl Protein

ENSP00000450607

InnateDB Gene

IDBG-41018 (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:17141802, ECO:0000269PubMed:17296725, ECO:0000269PubMed:23418588, ECO:0000269PubMed:9856465}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:17141802}.

Disease Associations

Tissue Specificity

Expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus and testis. Highest levels of expression in placenta, pancreas, thymus and testis. {ECO:0000269PubMed:9856465, ECO:0000269PubMed:9891984}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 25 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	25 [view]
Protein-Protein	21 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [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:0009582	detection of abiotic stimulus
GO:0009628	response to abiotic stimulus
GO:0030324	lung development
GO:0042752	regulation of circadian rhythm
GO:0044770	cell cycle phase transition
GO:0045892	negative regulation of transcription, DNA-templated
GO:0048754	branching morphogenesis of an epithelial tube