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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):
Expressed in all
HPA (cell line):
Mixed
HPA (normal tissue):
Mixed
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.
Reliability score (score description), divided into Supported, Approved, or Uncertain, is evaluated in normal tissues and based on consistency between the staining pattern of one antibody or several antibodies with RNA-seq data and available gene/protein characterization data.
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.
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.
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, the fraction of samples with protein expression level high, medium, low, or not detected are provided by the blue-scale color-coding (as described by the color-coding scale in the box to the left). The length of the bar represents the number of patient samples analyzed (max=12 patients). 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. The mouse-over function displays additional data for the features in the staining summary view.
Next to the cancer staining data, the protein expression data of normal tissues or specific cell types corresponding to each cancer are shown and protein expression levels are indicated by the blue-scale color coding.
A manually written summary of the overall protein expression pattern across the analyzed cancer tissues.
Moderate to strong cytoplasmic positivity was found in colorectal, breast, melanomas and gynaecological cancers. Remaining cancer tissues were generally negative.
A manually written summary of the overall protein expression pattern across the analyzed cancer tissues.
A majority of cancer tissues showed moderate to strong cytoplasmic and nuclear staining. Liver, pancreatic, renal, urothelial, testicular cancers were negative in a majority of cases.
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.
This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]
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) (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.
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.
Phobius predicted membrane proteins Predicted intracellular proteins Plasma proteins Cancer-related genes Mutated cancer genes Mutational cancer driver genes COSMIC somatic mutations in cancer genes COSMIC Splicing Mutations COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Large Deletions COSMIC Germline Mutations COSMIC Frameshift Mutations Protein evidence (Ezkurdia et al 2014)
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GO:0000209 [protein polyubiquitination] GO:0000422 [mitophagy] GO:0002039 [p53 binding] GO:0003677 [DNA binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005730 [nucleolus] GO:0005739 [mitochondrion] GO:0006351 [transcription, DNA-templated] GO:0006364 [rRNA processing] GO:0006469 [negative regulation of protein kinase activity] GO:0006915 [apoptotic process] GO:0006919 [activation of cysteine-type endopeptidase activity involved in apoptotic process] GO:0007050 [cell cycle arrest] GO:0008134 [transcription factor binding] GO:0008285 [negative regulation of cell proliferation] GO:0008637 [apoptotic mitochondrial changes] GO:0010389 [regulation of G2/M transition of mitotic cell cycle] GO:0016604 [nuclear body] GO:0016925 [protein sumoylation] GO:0030889 [negative regulation of B cell proliferation] GO:0031647 [regulation of protein stability] GO:0031648 [protein destabilization] GO:0033088 [negative regulation of immature T cell proliferation in thymus] GO:0033235 [positive regulation of protein sumoylation] GO:0043065 [positive regulation of apoptotic process] GO:0043234 [protein complex] GO:0043517 [positive regulation of DNA damage response, signal transduction by p53 class mediator] GO:0043687 [post-translational protein modification] GO:0044267 [cellular protein metabolic process] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0046825 [regulation of protein export from nucleus] GO:0048103 [somatic stem cell division] GO:0050821 [protein stabilization] GO:0051444 [negative regulation of ubiquitin-protein transferase activity] GO:0051882 [mitochondrial depolarization] GO:0055105 [ubiquitin-protein transferase inhibitor activity] GO:0070534 [protein K63-linked ubiquitination] GO:0071158 [positive regulation of cell cycle arrest] GO:0090398 [cellular senescence] GO:0097371 [MDM2/MDM4 family protein binding] GO:1900182 [positive regulation of protein localization to nucleus] GO:1901798 [positive regulation of signal transduction by p53 class mediator] GO:1902510 [regulation of apoptotic DNA fragmentation] GO:1903051 [negative regulation of proteolysis involved in cellular protein catabolic process] GO:1903214 [regulation of protein targeting to mitochondrion] GO:2000059 [negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process]
Phobius predicted membrane proteins Predicted intracellular proteins Plasma proteins Cancer-related genes Mutated cancer genes Mutational cancer driver genes COSMIC somatic mutations in cancer genes COSMIC Splicing Mutations COSMIC Somatic Mutations COSMIC Nonsense Mutations COSMIC Missense Mutations COSMIC Large Deletions COSMIC Germline Mutations COSMIC Frameshift Mutations Protein evidence (Ezkurdia et al 2014)
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GO:0000209 [protein polyubiquitination] GO:0000422 [mitophagy] GO:0002039 [p53 binding] GO:0003677 [DNA binding] GO:0005515 [protein binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005730 [nucleolus] GO:0005739 [mitochondrion] GO:0006351 [transcription, DNA-templated] GO:0006364 [rRNA processing] GO:0006469 [negative regulation of protein kinase activity] GO:0006915 [apoptotic process] GO:0006919 [activation of cysteine-type endopeptidase activity involved in apoptotic process] GO:0007050 [cell cycle arrest] GO:0008134 [transcription factor binding] GO:0008285 [negative regulation of cell proliferation] GO:0008637 [apoptotic mitochondrial changes] GO:0010389 [regulation of G2/M transition of mitotic cell cycle] GO:0016604 [nuclear body] GO:0016925 [protein sumoylation] GO:0030889 [negative regulation of B cell proliferation] GO:0031647 [regulation of protein stability] GO:0031648 [protein destabilization] GO:0033088 [negative regulation of immature T cell proliferation in thymus] GO:0033235 [positive regulation of protein sumoylation] GO:0043065 [positive regulation of apoptotic process] GO:0043234 [protein complex] GO:0043517 [positive regulation of DNA damage response, signal transduction by p53 class mediator] GO:0043687 [post-translational protein modification] GO:0044267 [cellular protein metabolic process] GO:0045893 [positive regulation of transcription, DNA-templated] GO:0045944 [positive regulation of transcription from RNA polymerase II promoter] GO:0046825 [regulation of protein export from nucleus] GO:0048103 [somatic stem cell division] GO:0050821 [protein stabilization] GO:0051444 [negative regulation of ubiquitin-protein transferase activity] GO:0051882 [mitochondrial depolarization] GO:0055105 [ubiquitin-protein transferase inhibitor activity] GO:0070534 [protein K63-linked ubiquitination] GO:0071158 [positive regulation of cell cycle arrest] GO:0090398 [cellular senescence] GO:0097371 [MDM2/MDM4 family protein binding] GO:1900182 [positive regulation of protein localization to nucleus] GO:1901798 [positive regulation of signal transduction by p53 class mediator] GO:1902510 [regulation of apoptotic DNA fragmentation] GO:1903051 [negative regulation of proteolysis involved in cellular protein catabolic process] GO:1903214 [regulation of protein targeting to mitochondrion] GO:2000059 [negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process]