Blood group antigen proteins Disease related genes FDA approved drug targets Plasma proteins Predicted secreted proteins
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
A summary of RNA categories for human tissues, cell lines and cancer tissues. Categories for RNA specificity include tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. Categories for RNA distribution include detected in single, detected in some, detected in many, detected in all and not detected.
Human tissue RNA category is based on the consensus dataset, which is a combination of RNA data from human tissues from three sources: HPA, GTEX and FANTOM5. Cell line RNA category is based on RNA data from cells lines from HPA dataset. More information can be found about the normalization and classification of these datasets.
Cancer tissue RNA category is based on RNA data from the The Cancer Genome Atlas (TCGA), categorized in the same way as human tissues and cell lines.
Group enriched (HDLM-2, HSkMC, U-266/70, U-266/84)
HPA (normal tissue):
Tissue enhanced (liver)
Evidence score for genes based on UniProt protein existence (UniProt evidence); a Human Protein Atlas antibody- or RNA based score (HPA evidence); and evidence based on PeptideAtlas (MS evidence). The avaliable scores are evidence at protein level, evidence at transcript level, no evidence, or not avaliable.
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 liver and positivity in plasma in several tissues.
IMMUNOHISTOCHEMISTRY DATA RELIABILITY
Data reliability descriptioni
Standardized explanatory sentences with additional information required for full understanding of the protein expression profile, based on knowledge-based and secretome-based annotation.
Caution, targets protein from more than one gene. Secreted protein, tissue location of RNA and protein might differ and correlation is complex. Presumed off target binding observed and disregarded.
Reliability score - normal tissuesi
A reliability score is manually set for all genes and indicates the level of reliability of the analyzed protein expression pattern based on available RNA-seq data, protein/gene characterization data and immunohistochemical data from one or several antibodies with non-overlapping epitopes. The reliability score is based on the 44 normal tissues analyzed, and if there is available data from more than one antibody, the staining patterns of all antibodies are taken into consideration during evaluation.
The reliability score is divided into Enhanced, Supported, Approved, or Uncertain, and is displayed on both Tissue Atlas and Pathology Atlas.
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 favorable or unfavorable 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).
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.Normal distribution across the dataset is visualized with box plots, shown as median and 25th and 75th percentiles. Points are displayed as outliers if they are above or below 1.5 times the interquartile range. 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: Tissue enhanced (liver cancer)
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.
Several cases of hepatocellular carcinomas, breast, endometrial, ovarian, prostate and thyroid cancers along with occasional cases of gliomas and renal cancers showed moderate to strong cytoplasmic and occasional membranous positivity. Remaining cancer tissues were weakly stained or negative.
Moderate granular cytoplasmic positivity was exhibited in several breast cancers along with gliomas, colorectal, cervical, lung, stomach and liver cancers. Several cases of prostate cancers were moderate to strongly stained. Remaining cancer tissues were negative.
Most tumour tissues displayed moderate to strong cytoplasmic and/or membranous positivity. Lymphomas along with several cases of gliomas, melanomas, endometrial, testicular and stomach cancers were negative.
Moderate immunoreactivity was observed in a few cases of breast, prostate, gastric and pancreatic cancers. Remaining cancer tissues generally showed weak cytoplasmic staining or were negative.
Distinct positivity was observed in plasma. Most malignant cells were negative although a few weakly stained cases were observed.
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 encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 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.
Below 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.
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.