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Protein class the gene product belongs to according to selected gene lists. List of protein classes.
Cancer-related genes CD markers Disease related genes FDA approved drug targets Predicted intracellular proteins Predicted membrane proteins Predicted secreted proteins
Predicted localizationi
Protein localization predicted from several bioinformatic algorithms.
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):
Mixed
HPA (cell line):
Cell line enhanced (HSkMC, NTERA-2)
HPA (normal tissue):
Tissue enhanced (lymph node)
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.
Cytoplasmic expression in a subset of immune cells in several tissues.
IMMUNOHISTOCHEMISTRY DATA RELIABILITY
Data reliability descriptioni
Standardized explanatory sentences with additional information required for full understanding of the knowledge-based expression profile.
Antibody staining mainly 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.
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.
A single case each of squamous cell carcinoma of skin and adenocarcinoma of endometrium exhibited strong cytoplasmic immunoreactivity. Remaining cancers were negative.
Few cases of melanomas and adenocarcinomas of lung, ovary and pancreatic cancers showed weak to moderate cytoplasmic staining. Most 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
TNFSF11 (HGNC Symbol)
Synonyms
CD254, ODF, OPGL, RANKL, TRANCE
Description
Tumor necrosis factor superfamily member 11 (HGNC Symbol)
Entrez gene summary
This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]
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.
TNFSF11-001
TNFSF11-002
TNFSF11-201
TNFSF11-202
TNFSF11-203
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.
O14788 [Direct mapping] Tumor necrosis factor ligand superfamily member 11 Tumor necrosis factor ligand superfamily member 11, membrane form Tumor necrosis factor ligand superfamily member 11, soluble form Q54A98 [Target identity:100%; Query identity:100%] Receptor activator of nuclear factor kappa B ligand 3; Tumor necrosis factor (Ligand) superfamily, member 11, isoform CRA_b
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CD markers Predicted intracellular proteins Cancer-related genes Candidate cancer biomarkers Disease related genes FDA approved drug targets Biotech drugs Small molecule drugs
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GO:0002548 [monocyte chemotaxis] GO:0005125 [cytokine activity] GO:0005164 [tumor necrosis factor receptor binding] GO:0005576 [extracellular region] GO:0005615 [extracellular space] GO:0005737 [cytoplasm] GO:0005886 [plasma membrane] GO:0005887 [integral component of plasma membrane] GO:0006955 [immune response] GO:0007275 [multicellular organism development] GO:0016020 [membrane] GO:0016021 [integral component of membrane] GO:0019221 [cytokine-mediated signaling pathway] GO:0019722 [calcium-mediated signaling] GO:0030154 [cell differentiation] GO:0030316 [osteoclast differentiation] GO:0032813 [tumor necrosis factor receptor superfamily binding] GO:0033209 [tumor necrosis factor-mediated signaling pathway] GO:0034112 [positive regulation of homotypic cell-cell adhesion] GO:0043406 [positive regulation of MAP kinase activity] GO:0045672 [positive regulation of osteoclast differentiation] GO:0045780 [positive regulation of bone resorption] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0050870 [positive regulation of T cell activation] GO:0051091 [positive regulation of sequence-specific DNA binding transcription factor activity] GO:0051092 [positive regulation of NF-kappaB transcription factor activity] GO:0051466 [positive regulation of corticotropin-releasing hormone secretion] GO:0071812 [positive regulation of fever generation by positive regulation of prostaglandin secretion] GO:0071847 [TNFSF11-mediated signaling pathway] GO:0071848 [positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling] GO:1902533 [positive regulation of intracellular signal transduction]
O14788 [Direct mapping] Tumor necrosis factor ligand superfamily member 11 Tumor necrosis factor ligand superfamily member 11, membrane form Tumor necrosis factor ligand superfamily member 11, soluble form Q54A98 [Target identity:100%; Query identity:100%] Receptor activator of nuclear factor kappa B ligand 3; Tumor necrosis factor (Ligand) superfamily, member 11, isoform CRA_b
Show all
CD markers Predicted intracellular proteins Cancer-related genes Candidate cancer biomarkers Disease related genes FDA approved drug targets Biotech drugs Small molecule drugs
Show all
GO:0002548 [monocyte chemotaxis] GO:0005125 [cytokine activity] GO:0005164 [tumor necrosis factor receptor binding] GO:0005576 [extracellular region] GO:0005615 [extracellular space] GO:0005737 [cytoplasm] GO:0005886 [plasma membrane] GO:0005887 [integral component of plasma membrane] GO:0006955 [immune response] GO:0007275 [multicellular organism development] GO:0016020 [membrane] GO:0016021 [integral component of membrane] GO:0019221 [cytokine-mediated signaling pathway] GO:0019722 [calcium-mediated signaling] GO:0030154 [cell differentiation] GO:0030316 [osteoclast differentiation] GO:0032813 [tumor necrosis factor receptor superfamily binding] GO:0033209 [tumor necrosis factor-mediated signaling pathway] GO:0034112 [positive regulation of homotypic cell-cell adhesion] GO:0043406 [positive regulation of MAP kinase activity] GO:0045672 [positive regulation of osteoclast differentiation] GO:0045780 [positive regulation of bone resorption] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0050870 [positive regulation of T cell activation] GO:0051091 [positive regulation of sequence-specific DNA binding transcription factor activity] GO:0051092 [positive regulation of NF-kappaB transcription factor activity] GO:0051466 [positive regulation of corticotropin-releasing hormone secretion] GO:0071812 [positive regulation of fever generation by positive regulation of prostaglandin secretion] GO:0071847 [TNFSF11-mediated signaling pathway] GO:0071848 [positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling] GO:1902533 [positive regulation of intracellular signal transduction]
O14788 [Direct mapping] Tumor necrosis factor ligand superfamily member 11 Tumor necrosis factor ligand superfamily member 11, membrane form Tumor necrosis factor ligand superfamily member 11, soluble form Q54A98 [Target identity:100%; Query identity:100%] Receptor activator of nuclear factor kappa B ligand 3; Tumor necrosis factor (Ligand) superfamily, member 11, isoform CRA_b
Show all
CD markers Predicted intracellular proteins Cancer-related genes Candidate cancer biomarkers Disease related genes FDA approved drug targets Biotech drugs Small molecule drugs
Show all
GO:0002548 [monocyte chemotaxis] GO:0005125 [cytokine activity] GO:0005164 [tumor necrosis factor receptor binding] GO:0005576 [extracellular region] GO:0005615 [extracellular space] GO:0005737 [cytoplasm] GO:0005886 [plasma membrane] GO:0005887 [integral component of plasma membrane] GO:0006955 [immune response] GO:0007275 [multicellular organism development] GO:0016020 [membrane] GO:0016021 [integral component of membrane] GO:0019221 [cytokine-mediated signaling pathway] GO:0019722 [calcium-mediated signaling] GO:0030154 [cell differentiation] GO:0030316 [osteoclast differentiation] GO:0032813 [tumor necrosis factor receptor superfamily binding] GO:0033209 [tumor necrosis factor-mediated signaling pathway] GO:0034112 [positive regulation of homotypic cell-cell adhesion] GO:0043406 [positive regulation of MAP kinase activity] GO:0045672 [positive regulation of osteoclast differentiation] GO:0045780 [positive regulation of bone resorption] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0050870 [positive regulation of T cell activation] GO:0051091 [positive regulation of sequence-specific DNA binding transcription factor activity] GO:0051092 [positive regulation of NF-kappaB transcription factor activity] GO:0051466 [positive regulation of corticotropin-releasing hormone secretion] GO:0071812 [positive regulation of fever generation by positive regulation of prostaglandin secretion] GO:0071847 [TNFSF11-mediated signaling pathway] GO:0071848 [positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling] GO:1902533 [positive regulation of intracellular signal transduction]
The Human Protein Atlas project is funded
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