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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):
Mixed
HPA (cell line):
Cell line enhanced (A-431, RH-30)
HPA (normal tissue):
Tissue enriched (parathyroid 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.
Estimation of protein expression could not be performed. View primary data.
IMMUNOHISTOCHEMISTRY DATA RELIABILITY
Data reliability descriptioni
Standardized explanatory sentences with additional information required for full understanding of the knowledge-based expression profile.
RNA-based expert annotation gave inconclusive results. Pending external verification.
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.
Weak to moderate immunoreactivity was observed in colorectal, breast, prostate, cervical, skin, urothelial and liver cancers. Remaining cancers were mainly 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
SIX4 (HGNC Symbol)
Synonyms
AREC3
Description
SIX homeobox 4 (HGNC Symbol)
Entrez gene summary
This gene encodes a member of the homeobox family, subfamily SIX. The drosophila homolog is a nuclear homeoprotein required for eye development. Studies in mouse show that this gene product functions as a transcription factor, and may have a role in the differentiation or maturation of neuronal cells. [provided by RefSeq, May 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.
SIX4-001
SIX4-004
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 Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000978 [RNA polymerase II core promoter proximal region sequence-specific DNA binding] GO:0001077 [transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding] GO:0003677 [DNA binding] GO:0003700 [transcription factor activity, sequence-specific DNA binding] GO:0005634 [nucleus] GO:0005737 [cytoplasm] GO:0006351 [transcription, DNA-templated] GO:0006355 [regulation of transcription, DNA-templated] GO:0006366 [transcription from RNA polymerase II promoter] GO:0007275 [multicellular organism development] GO:0007519 [skeletal muscle tissue development] GO:0008582 [regulation of synaptic growth at neuromuscular junction] GO:0008584 [male gonad development] GO:0009653 [anatomical structure morphogenesis] GO:0010468 [regulation of gene expression] GO:0030238 [male sex determination] GO:0030910 [olfactory placode formation] GO:0032880 [regulation of protein localization] GO:0034504 [protein localization to nucleus] GO:0042472 [inner ear morphogenesis] GO:0043066 [negative regulation of apoptotic process] GO:0043524 [negative regulation of neuron apoptotic process] GO:0043565 [sequence-specific DNA binding] GO:0043586 [tongue development] GO:0045214 [sarcomere organization] 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:0046661 [male sex differentiation] GO:0048538 [thymus development] GO:0048699 [generation of neurons] GO:0048701 [embryonic cranial skeleton morphogenesis] GO:0048704 [embryonic skeletal system morphogenesis] GO:0048856 [anatomical structure development] GO:0050678 [regulation of epithelial cell proliferation] GO:0051451 [myoblast migration] GO:0060037 [pharyngeal system development] GO:0061055 [myotome development] GO:0061197 [fungiform papilla morphogenesis] GO:0061551 [trigeminal ganglion development] GO:0072075 [metanephric mesenchyme development] GO:0072095 [regulation of branch elongation involved in ureteric bud branching] GO:0072107 [positive regulation of ureteric bud formation] GO:0090190 [positive regulation of branching involved in ureteric bud morphogenesis] GO:0098528 [skeletal muscle fiber differentiation] GO:1902725 [negative regulation of satellite cell differentiation]
The Human Protein Atlas project is funded
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