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Show complete data for human cells assay. The location(s) are highlighted in the illustration on the right.
Mainly localized to the nucleus. In addition localized to the nucleoli.
RNA cell categoryi
The cell lines in the Human Protein Atlas have been analyzed by RNA-seq to estimate the transcript abundance of each protein-coding gene. The RNA-seq data was then used to classify all genes according to their cell line-specific expression into one of six different categories, defined based on the total set of all TPM values in all analyzed cell lines.
Protein evidence scores are generated from several independent sources and are classified as evidence at i) protein level, ii) transcript level, iii) no evidence, or iv) not available.
Evidence at protein level
Main locationi
The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations. It is highlighted in the illustration to the right. If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively.
Localized to the Nucleus (supported)
Additional locationi
Additional locations are characterized by either a markedly lower staining intensity than the main location, or that it is only observed in a subset of the cell lines. They are highlighted in the illustration to the right. If available, links to overrepresentation analyses in Reactome, a free, open-source, curated and peer reviewed biological pathway database, are provided. An analysis is done for the corresponding gene set of the proteome localizing to the main and additional locations of the protein on this page, respectively.
In addition localized to the Nucleoli (approved)
Single-cell variationi
As the images in the Cell Atlas provide single cell resolution, variations in protein expression patterns from cell to cell can be observed. A single-cell variation can either be observed in the intensity of the immunofluorescent signal or in the spatial distribution pattern of the protein. Show complete data for single-cell variation.
Single-cell variation in protein expression observed.
Cell cycle dependent expression determined by custom assay
DATA RELIABILITY
Reliability scorei
A reliability score is set for all genes and indicates the level of reliability of the analyzed protein expression pattern based on available protein/RNA/gene characterization data. The reliability of the annotated protein expression data is also scored depending on similarity in immunostaining patterns and consistency with available experimental gene/protein characterization data in the UniProtKB/Swiss-Prot database.
Below is an overview of RNA expression data generated in the HPA project. The analyzed cell lines are divided into 12 color-coded groups according to the organ they were obtained from. By clicking the toolbars in the top right corner it is possible to sort the cell lines in the chart by different criteria: the organ and the origin that the cell line was obtained from, the category of the cell line according to cellosaurus, alphabetically or by descending RNA expression. Detailed information about a specific cell line can be accessed by hovering over the corresponding bar in the chart. The RNA-sequencing results generated in the HPA are reported as number of Transcripts per Kilobase Million (TPM). In the Human Protein Atlas a TPM value of 1.0 is defined as a treshhold for expression of the corresponding protein.
The cell lines in the Human Protein Atlas have been analyzed by RNA-seq to estimate the transcript abundance of each protein-coding gene. The RNA-seq data was then used to classify all genes according to their cell line-specific expression into one of six different categories, defined based on the total set of all TPM values in all analyzed cell lines.
Cell lines sorted after organ of phenotypic resemblance.
Cell lines sorted after biological source for establishment.
Cell lines sorted after the cell line category according to Cellosaurus.
Cell lines sorted on descending RNA expression.
Cell lines sorted alphabetically.
HUMAN CELLSi
The "human cells" section gives an overview about the subcellular location of the protein of interest obtained by indirect immunofluorescence microscopy, an antibody-based protein-visualization technique. The immunofluorescent analysis is carried out in three different cell lines, one of them always being U-2 OS. A selection of immunofluorescent images is displayed below. Three different organelle probes are displayed as different channels in the multicolor images - nucleus stained in blue, microtubules in red and ER in yellow. The antibody staining targeting the protein of interest is shown in green. By using the toggle channel buttons, the different channels can be turned on and off. For the selection of the images to compare, use the checkboxes next to the images at the bottom. Three images can be compared at a time. All images are clickable for an enlarged view. The selected image will appear in large size and miniature images with all other staining results for this gene will be listed at the top left of the image. The selected miniature image has an orange overlay. For cell structure reference, visit the cell dictionary.
Summaryi
Summary of the immunofluorescent analysis in all studied cell lines with all tested antibodies.
Mainly localized to the nucleus. In addition localized to the nucleoli.
Main locationi
The main location is characterized by presence in all tested cell lines and/or increased intensity compared to other locations.
Nucleus (supported)
Additional locationi
Additional locations are characterized by either a markedly lower staining intensity than the main location, or that it is only observed in a subset of the cell lines.
Nucleoli (approved)
Toggle channelsi
Three different organelle probes are displayed as different channels in the multicolor images - nucleus stained in blue, microtubules in red and ER in yellow. The antibody staining targeting the protein of interest is shown in green. By using the "toggle channels"-buttons, the different channels can be turned on and off. The intensity toggle shows the pixel intensity range in 16 different colors for the selected channel. The object toggle shows the computational segmentation of the cells used for further analysis in the HPA project. For samples where cell cycle dependency for the protein is suggested according to a correlation assay the predicted cell cycle position of each cell is displayed when using the object toggle.
Low
High
G1
S
G2
M
N/A
Thumbnaili
Representative images for the assay. Three images can be compared at the same time. To change which images to compare, use the checkboxes next to the images below. All images are clickable for an enlarged view. The selected image will appear in large size and miniature images with all other staining results for this gene will be listed at the top left of the image. The selected miniature image has an orange overlay.
Antibodyi
Antibody used for analysis. Clicking the antibody ID links to the antibody validation page.
Cell linei
Cell line used for analysis. Read more about the cell lines in the Human Protein Atlas.
Locationi
Location(s) annotated in the corresponding cell line.
Single-cell variationi
As the images in the Cell Atlas provide single cell resolution, variations in protein expression patterns from cell to cell can be observed. A single-cell variation can either be observed in the intensity of the immunofluorescent signal or in the spatial distribution pattern of the protein. This column contains information about whether and for which of the annotated locations a single-cell variation pattern was manually annotated.
Cell cycle dependent variationi
A likely cause for single-cell variation in the immunofluorescent images is cell cycle dependency. This column contains information about whether the manually observed cell-to-cell variation pattern correlates with cell cycle progression.
The custom data section contains information about experiments that were carried out by researchers in the Cell Atlas independent of the general workflow in the project. This includes but is not limited to colocalization experiments with known organelle markers or stainings of proteins in the cell cycle marker cell line U-2 OS FUCCI (Fluorescence Ubiquitination Cell Cycle Indicator). Example images as well as a detailed description of the respective assay are provided. Different organelle probes are displayed as different channels in the multicolor images. By using the "toggle channels"-buttons, the different channels can be turned on and off. To change which images to compare, use the checkboxes next to the images at the bottom. Three images can be compared at a time. All images are clickable for an enlarged view. The selected image will appear in large size and miniature images with all other staining results for this gene will be listed at the top left of the image. The selected miniature image has an orange overlay. If a movie is available click the thumbnail in order to show the video clip.
Toggle channelsi
By using the "toggle channels"-buttons, the different channels can be turned on and off.
Thumbnaili
Representative images for the assay. Three images can be compared at the same time. To change which images to compare, use the checkboxes next to the images below. All images are clickable for an enlarged view. The selected image will appear in large size and miniature images with all other staining results for this gene will be listed at the top left of the image. The selected miniature image has an orange overlay.
Antibodyi
Antibody used for analysis. Clicking the antibody ID links to the antibody validation page.
Cell linei
Cell line used for analysis. Read more about the cell lines in the Human Protein Atlas.
Assayi
Depending on the type of custom data the assay can be an immunofluorescent image, an immunofluorescent image stack, siRNA validation data or a time-lapse movie.
Staining of U 2-OS FUCCI cells, to characterize the cell cycle dependency of the protein expression pattern. The FUCCI cells, Fluorescence Ubiquitination Cell Cycle Indicator, are cells tagged with different fluorescent proteins fused to two different cell cycle regulators Cdt1 (expressed in G1 phase) and Geminin (expressed in S and G2 phases) that allows cell cycle monitoring. When both proteins are present, the overlay of the images appear in yellow marking the G1/S transition. TOP2A is mostly expressed during S and/or G2, and during Mitosis.
CELL CYCLEi
As the images in the Cell Atlas provide single cell resolution, variations in protein expression patterns from cell to cell can be observed. A single-cell variation can either be observed in the intensity of the immunofluorescent signal or in the spatial distribution pattern of the protein. Since the cells are grown under asynchronous conditions the most likely explanation for this would be cell cycle effects. However, to confirm the cell cycle dependency of a protein additional approaches are required. This can be done by staining the protein in the cell cycle marker cell line U-2 OS FUCCI (Fluorescence Ubiquitination Cell Cycle Indicator). Another approach uses a computational model to infer the cell cycle position of the cells in the image which allows the pattern of cell cycle dependency to be determined. Lastly, proteins localizing to structures that are cell cycle dependent by biological definition (e.g. mitotic spindle, cytokinetic bridge) are labeled as cell cycle dependent in the Cell Atlas.
Expression has cell cycle dependency according to custom assay
Intensity variationi
Location(s) where a cell-to-cell variation correlates with cell cycle progression.
Nucleoli, Nucleus
GENE INFORMATIONi
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Gene name
TOP2A (HGNC Symbol)
Synonyms
TOP2
Description
Topoisomerase (DNA) II alpha (HGNC Symbol)
Entrez gene summary
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. [provided by RefSeq, Jul 2010]
The protein browser displays the antigen location on the target protein(s) and the features of the target protein. The tabs at the top of the protein view section can be used to switch between the different splice variants to which an antigen has been mapped.
At the top of the view, the position of the antigen (identified by the corresponding HPA identifier) is shown as a green bar. A yellow triangle on the bar indicates a <100% sequence identity to the protein target.
Under the antigens, the maximum percent sequence identity of the protein to all other proteins from other human genes is displayed, using a sliding window of 10 aa residues (HsID 10) or 50 aa residues (HsID 50). The region with the lowest possible identity is always selected for antigen design, with a maximum identity of 60% allowed for designing a single-target antigen (read more).
The curve in blue displays the predicted antigenicity i.e. the tendency for different regions of the protein to generate an immune response, with peak regions being predicted to be more antigenic.The curve shows average values based on a sliding window approach using an in-house propensity scale. (read more).
If a signal peptide is predicted by a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius (turquoise) and/or transmembrane regions (orange) are predicted by MDM, these are displayed.
Low complexity regions are shown in yellow and InterPro regions in green. Common (purple) and unique (grey) regions between different splice variants of the gene are also displayed (read more), and at the bottom of the protein view is the protein scale.
TOP2A-001
TOP2A-003
TOP2A-006
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The ENSP identifier links to the Ensembl website protein summary, while the ENST identifier links to the Ensembl website transcript summary for the selected splice variant. The data in the UniProt column can be expanded to show links to all matching UniProt identifiers for this protein.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The Gene Ontology terms assigned to this protein are listed if expanding the Gene ontology column. The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide (according to a majority of the signal peptide predictors SPOCTOPUS, SignalP 4.0, and Phobius) and the number of predicted transmembrane region(s) (according to MDM) are also reported.
Enzymes ENZYME proteins Isomerase Predicted intracellular proteins Plasma proteins Cancer-related genes Candidate cancer biomarkers FDA approved drug targets Small molecule drugs Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
The Human Protein Atlas project is funded
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