TIMELESS protein expression summary - The Human Protein Atlas

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TIMELESS

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STRUCT & INT

TIMELESS

TIMELESS INFORMATION
Proteinⁱ Full gene name according to HGNC.	Timeless circadian regulator
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	TIMELESS (hTIM, TIM, TIM1)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s).	Disease related genes
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	2
Protein interactions	Interacting with 2 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	Nuclear expression in several tissues.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Nucleoplasm
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.	Intracellular

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Low tissue specificity
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Transcription (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Low human brain regional specificity
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Oligodendrocytes - Mixed function (mainly)

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Cell type enhanced (Bipolar cells, Spermatogonia)
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Cell proliferation (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched (Skin - Mitotic cells (Skin), Stomach - Mitotic cells (Stomach), Testis - Spermatogonia)
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Low immune cell specificity
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Unknown function (mainly)

CANCER & CELL LINES
Prognostic summary	TIMELESS is a prognostic marker in Kidney chromophobe, Liver hepatocellular carcinoma, Lung adenocarcinoma, Skin cuteneous melanoma
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Low cancer specificity
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Non-specific - Transcription (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Low cancer specificity

PROTEINS IN BLOOD
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	No
Proximity extension assayⁱ Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years. Read more	Not available

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock 1, 2, 3, 4, 5, 6, 7, 8, 9. Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: 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 10, 11, 12, 13. During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis 14. TIMELESS promotes TIPIN nuclear localization 15, 16. Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 17. Involved in cell survival after DNA damage or replication stress by promoting DNA repair 18, 19, 20, 21. In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 22, 23, 24. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light 25. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock 26, 27. Negatively regulates CLOCK\|NPAS2-ARTNL/BMAL1\|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus 28, 29. May play a role as destabilizer of the PER2-CRY2 complex 30. May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity).... show less
Molecular function (UniProt)ⁱ Keywords assigned by UniProt to proteins due to their particular molecular function.	Developmental protein
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Biological rhythms, Cell cycle, Cell division, DNA damage, DNA repair, Mitosis, Transcription, Transcription regulation
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]... show less

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