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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):
Group enriched (HBEC3-KT, LHCN-M2, RH-30)
HPA (normal tissue):
Expressed in all
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.
Mainly nuclear but also cytoplasmic expression at variable levels in most 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. Presumed off target binding observed and disregarded.
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.
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.
Nuclear staining of varying intensities, often with additional cytoplasmic positivity, was observed in all cancers.
Most cancers displayed nuclear positivity at variable intensities, with additional cytoplasmic staining in several 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.
Gene name
CDK4 (HGNC Symbol)
Synonyms
PSK-J3
Description
Cyclin dependent kinase 4 (HGNC Symbol)
Entrez gene summary
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [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.
CDK4-001
CDK4-004
CDK4-005
CDK4-006
CDK4-007
CDK4-009
CDK4-010
CDK4-011
CDK4-012
CDK4-201
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 Transferases Kinases CMGC Ser/Thr protein kinases MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Plasma proteins Cancer-related genes Candidate cancer biomarkers Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Disease related genes FDA approved drug targets Small molecule drugs Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000082 [G1/S transition of mitotic cell cycle] GO:0000166 [nucleotide binding] GO:0000307 [cyclin-dependent protein kinase holoenzyme complex] GO:0000785 [chromatin] GO:0002088 [lens development in camera-type eye] GO:0004672 [protein kinase activity] GO:0004674 [protein serine/threonine kinase activity] GO:0004693 [cyclin-dependent protein serine/threonine kinase activity] GO:0005515 [protein binding] GO:0005524 [ATP binding] GO:0005634 [nucleus] GO:0005654 [nucleoplasm] GO:0005667 [transcription factor complex] GO:0005730 [nucleolus] GO:0005737 [cytoplasm] GO:0005829 [cytosol] GO:0005923 [bicellular tight junction] GO:0006468 [protein phosphorylation] GO:0007049 [cell cycle] GO:0007165 [signal transduction] GO:0007275 [multicellular organism development] GO:0007623 [circadian rhythm] GO:0008284 [positive regulation of cell proliferation] GO:0009636 [response to toxic substance] GO:0010033 [response to organic substance] GO:0010288 [response to lead ion] GO:0010468 [regulation of gene expression] GO:0010971 [positive regulation of G2/M transition of mitotic cell cycle] GO:0016020 [membrane] GO:0016301 [kinase activity] GO:0016310 [phosphorylation] GO:0016538 [cyclin-dependent protein serine/threonine kinase regulator activity] GO:0016740 [transferase activity] GO:0030332 [cyclin binding] GO:0031100 [animal organ regeneration] GO:0031965 [nuclear membrane] GO:0032403 [protein complex binding] GO:0032869 [cellular response to insulin stimulus] GO:0033574 [response to testosterone] GO:0040014 [regulation of multicellular organism growth] GO:0042127 [regulation of cell proliferation] GO:0042493 [response to drug] GO:0043065 [positive regulation of apoptotic process] GO:0043234 [protein complex] GO:0045727 [positive regulation of translation] GO:0045787 [positive regulation of cell cycle] GO:0045793 [positive regulation of cell size] GO:0045859 [regulation of protein kinase activity] GO:0046626 [regulation of insulin receptor signaling pathway] GO:0046890 [regulation of lipid biosynthetic process] GO:0048146 [positive regulation of fibroblast proliferation] GO:0048471 [perinuclear region of cytoplasm] GO:0050994 [regulation of lipid catabolic process] GO:0051301 [cell division] GO:0051726 [regulation of cell cycle] GO:0055093 [response to hyperoxia] GO:0060612 [adipose tissue development] GO:0071157 [negative regulation of cell cycle arrest] GO:0071222 [cellular response to lipopolysaccharide] GO:0071353 [cellular response to interleukin-4] GO:0097129 [cyclin D2-CDK4 complex] GO:1904628 [cellular response to phorbol 13-acetate 12-myristate] GO:1904637 [cellular response to ionomycin]
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Cancer-related genes Mutated cancer genes COSMIC somatic mutations in cancer genes COSMIC Missense Mutations COSMIC Germline Mutations Protein evidence (Ezkurdia et al 2014)
The Human Protein Atlas project is funded
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