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RNA category is based on mRNA expression levels in the analyzed samples (RNA assay description). The categories include: tissue/cell line enriched, group enriched, tissue/cell line enhanced, expressed in all, mixed and not detected. RNA category is calculated separately for The Cancer Genome Atlas (TCGA) data from cancer tissues and internally generated Human Protein Atlas (HPA) data from normal tissues and cell lines.
TCGA (cancer tissue):
Group enriched (lung cancer, thyroid cancer)
HPA (cell line):
Cell line enriched (SCLC-21H)
HPA (normal tissue):
Group enriched (lung, thyroid gland)
Protein evidencei
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
Protein expression normal tissuei
A summary of the overall protein expression pattern across the analyzed normal tissues. The summary is based on knowledge-based annotation.
"Estimation of protein expression could not be performed. View primary data." is shown for genes analyzed with a knowledge-based approach where available RNA-seq and gene/protein characterization data has been evaluated as not sufficient in combination with immunohistochemistry data to yield a reliable estimation of the protein expression profile.
Standardized explanatory sentences with additional information required for full understanding of the knowledge-based expression profile.
Antibody staining consistent with RNA expression data.
Reliability score - normal tissuesi
Reliability score (score description), divided into Enhanced, Supported, Approved, or Uncertain, is evaluated in normal tissues and based on consistency between antibody staining pattern, available RNA-Seq and gene/protein characterization data, as well as similarity between independent antibodies targeting the same protein.
Kaplan-Meier plots for all cancers where high expression of this gene has significant (p<0.001) association with patient survival are shown in this summary. Whether the prognosis is favourable or unfavourable is indicated in brackets. Each Kaplan-Meier plot is clickable and redirects to a detailed page that includes individual expression and survival data for patients with the selected cancer.
Gene product is not prognostic.
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RNA EXPRESSION OVERVIEWi
RNA expression overview shows RNA-seq data from The Cancer Genome Atlas (TCGA).
TCGA dataseti
RNA-seq data in 17 cancer types are reported as median FPKM (number Fragments Per Kilobase of exon per Million reads), generated by the The Cancer Genome Atlas (TCGA). RNA cancer tissue category is calculated based on mRNA expression levels across all 17 cancer tissues and include: cancer tissue enriched, cancer group enriched, cancer tissue enhanced, expressed in all, mixed and not detected. To access cancer specific RNA and prognostic data, click on the cancer name. The cancer types are color-coded according to which type of normal organ the cancer originates from.
RNA cancer category: Group enriched (lung cancer, thyroid cancer)
PROTEIN EXPRESSIONi
Antibody staining in 20 different cancers is summarized by a selection of four standard cancer tissue samples representative of the overall staining pattern. From left: colorectal cancer, breast cancer, prostate cancer and lung cancer. An additional fifth image can be added as a complement. The assay and annotation is described here. Note that samples used for immunohistochemistry by the Human Protein Atlas do not correspond to samples in the TCGA dataset.
For each cancer, color-coded bars indicate the percentage of patients (maximum 12 patients) with high and medium protein expression level. The cancer types are color-coded according to which type of normal organ the cancer originates from. Low or not detected protein expression results in a white bar. Mouse-over function shows details about expression level and normal tissue of origin. The images and annotations can be accessed by clicking on the cancer name or protein expression bar. If more than one antibody is analyzed, the tabs at the top of the staining summary section can be used to toggle between the different antibodies.
Thyroid and lung cancers showed moderate to strong nuclear positivity. Remaining cancers were negative.
Papillary adenocarcinomas of thyroid, lung adenocarcinomas and a single case of carcinoid showed strong nuclear staining. Remaining cancers were negative.
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
NKX2-1 (HGNC Symbol)
Synonyms
BCH, NKX2A, TITF1, TTF-1, TTF1
Description
NK2 homeobox 1 (HGNC Symbol)
Entrez gene summary
This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]
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.
NKX2-1-001
NKX2-1-002
NKX2-1-003
NKX2-1-004
NKX2-1-005
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.
Predicted intracellular proteins Transcription factors Helix-turn-helix domains Cancer-related genes COSMIC somatic mutations in cancer genes COSMIC Amplifications COSMIC Somatic Mutations Disease related genes Protein evidence (Kim et al 2014)
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GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] GO:0000977 [RNA polymerase II regulatory region sequence-specific DNA binding] GO:0001012 [RNA polymerase II regulatory region DNA binding] GO:0001047 [core promoter binding] GO:0001161 [intronic transcription regulatory region sequence-specific DNA binding] GO:0003677 [DNA binding] GO:0003700 [transcription factor activity, sequence-specific DNA binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0006351 [transcription, DNA-templated] GO:0006355 [regulation of transcription, DNA-templated] GO:0007420 [brain development] GO:0009725 [response to hormone] GO:0010628 [positive regulation of gene expression] GO:0010719 [negative regulation of epithelial to mesenchymal transition] GO:0019899 [enzyme binding] GO:0021759 [globus pallidus development] GO:0030324 [lung development] GO:0030336 [negative regulation of cell migration] GO:0030512 [negative regulation of transforming growth factor beta receptor signaling pathway] GO:0030878 [thyroid gland development] GO:0030900 [forebrain development] GO:0042753 [positive regulation of circadian rhythm] GO:0043565 [sequence-specific DNA binding] GO:0044212 [transcription regulatory region DNA binding] GO:0044213 [intronic transcription regulatory region DNA binding] GO:0045892 [negative regulation of transcription, DNA-templated] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0048511 [rhythmic process] GO:0060441 [epithelial tube branching involved in lung morphogenesis]
Predicted intracellular proteins Transcription factors Helix-turn-helix domains Cancer-related genes COSMIC somatic mutations in cancer genes COSMIC Amplifications COSMIC Somatic Mutations Disease related genes Protein evidence (Kim et al 2014)
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GO:0000122 [negative regulation of transcription from RNA polymerase II promoter] GO:0000977 [RNA polymerase II regulatory region sequence-specific DNA binding] GO:0001012 [RNA polymerase II regulatory region DNA binding] GO:0001047 [core promoter binding] GO:0001161 [intronic transcription regulatory region sequence-specific DNA binding] GO:0001764 [neuron migration] GO:0003677 [DNA binding] GO:0003700 [transcription factor activity, sequence-specific DNA binding] GO:0003705 [transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005667 [transcription factor complex] GO:0006351 [transcription, DNA-templated] GO:0006355 [regulation of transcription, DNA-templated] GO:0006357 [regulation of transcription from RNA polymerase II promoter] GO:0006644 [phospholipid metabolic process] GO:0007389 [pattern specification process] GO:0007411 [axon guidance] GO:0007420 [brain development] GO:0007492 [endoderm development] GO:0007626 [locomotory behavior] GO:0009725 [response to hormone] GO:0009887 [animal organ morphogenesis] GO:0010628 [positive regulation of gene expression] GO:0010719 [negative regulation of epithelial to mesenchymal transition] GO:0019899 [enzyme binding] GO:0021537 [telencephalon development] GO:0021759 [globus pallidus development] GO:0021766 [hippocampus development] GO:0021795 [cerebral cortex cell migration] GO:0021798 [forebrain dorsal/ventral pattern formation] GO:0021877 [forebrain neuron fate commitment] GO:0021879 [forebrain neuron differentiation] GO:0021892 [cerebral cortex GABAergic interneuron differentiation] GO:0021895 [cerebral cortex neuron differentiation] GO:0021983 [pituitary gland development] GO:0022029 [telencephalon cell migration] GO:0030324 [lung development] GO:0030336 [negative regulation of cell migration] GO:0030512 [negative regulation of transforming growth factor beta receptor signaling pathway] GO:0030878 [thyroid gland development] GO:0030900 [forebrain development] GO:0031128 [developmental induction] GO:0033327 [Leydig cell differentiation] GO:0042753 [positive regulation of circadian rhythm] GO:0043565 [sequence-specific DNA binding] GO:0044212 [transcription regulatory region DNA binding] GO:0044213 [intronic transcription regulatory region DNA binding] GO:0045892 [negative regulation of transcription, DNA-templated] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0048511 [rhythmic process] GO:0048646 [anatomical structure formation involved in morphogenesis] GO:0048663 [neuron fate commitment] GO:0048709 [oligodendrocyte differentiation] GO:0060430 [lung saccule development] GO:0060441 [epithelial tube branching involved in lung morphogenesis] GO:0060486 [Clara cell differentiation] GO:0060510 [Type II pneumocyte differentiation]
The Human Protein Atlas project is funded
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