AGER protein expression summary - The Human Protein Atlas

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AGER

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STRUCT & INT

AGER

AGER INFORMATION
Proteinⁱ Full gene name according to HGNC.	Advanced glycosylation end-product specific receptor
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	AGER (RAGE, SCARJ1, sRAGE)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s).	Cancer-related genes Plasma proteins Transporters
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	9
Protein interactions	Interacting with 12 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	Membranous expression in pneumocytes. Weak expression in endothelial cells.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Plasma membrane, Cell Junctions In addition localized to the Nucleoli fibrillar center
Predicted locationⁱ 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.	Secreted, Membrane (different isoforms)
Extracellular locationⁱ All genes with at least one isoform expected to be secreted to the extracellular environment have been annotated and classified either as secreted to blood or as locally secreted, depending on the predicted final location of the corresponding protein. Proteins expected to be locally secreted have been further classified according to their site of expression.	Locally secreted

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Tissue enriched (Lung)
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Lung - Lung function (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Not detected in human brain
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Not detected - no cluster assigned

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Cell type enriched (Alveolar cells type 1)
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Alveolar cells - Lung function (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched (Lung - Alveolar cells type 1)
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Not detected in immune cells
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Not detected - no cluster assigned

CANCER & CELL LINES
Prognostic summary	AGER is a prognostic marker in Ovary serous cystadenocarcinoma, Pancreatic adenocarcinoma
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Group enriched (Lung Adenocarcinoma, Lung Squamous Cell Carcinoma, Thyroid Carcinoma)
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Kidney cancer - Membrane components (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Cancer enhanced (Kidney cancer)

PROTEINS IN BLOOD
Upregulated in diseaseⁱ A gene is classified as upregulated in a disease if the average concentration of all samples of that disease is significantly higher (adj P-value<0.005 and NPX difference>=1) than the average concentration of samples of all diseases as measured by PEA . For gender specific diseases the analysis includes only samples corresponding to the same gender from the other diseases.	Pediatric retinoblastoma, Pediatric neuroblastoma
Disease prediction modelⁱ The disease(s) the gene is associated with and able to predict according to glmnet prediction models. To be included the gene has to be upregulated according to differential expression analysis and have more than 50% overall importance as indicated by the prediction models.	Viral hepatitis related cirrhosis (Class,All other diseases), Cervical cancer (Class)
Secretome annotationⁱ All genes with at least one predicted secreted isoform have been annotated and classified with the aim to determine if the corresponding protein(s) are: secreted into blood locally secreted or actually being attached to membrane or retained in intracellular locations like mitochondria, endoplasmatic reticulum (ER), Golgi apparatus or lysosomes.	Locally secreted
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	Yes
Proximity extension assayⁱ Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years. Read more	Data available (High detectability)

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Cell surface pattern recognition receptor that senses endogenous stress signals with a broad ligand repertoire including advanced glycation end products, S100 proteins, high-mobility group box 1 protein/HMGB1, amyloid beta/APP oligomers, nucleic acids, phospholipids and glycosaminoglycans 1, 2, 3. Advanced glycosylation end products are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes 4. These ligands accumulate at inflammatory sites during the pathogenesis of various diseases, including diabetes, vascular complications, neurodegenerative disorders, and cancers and RAGE transduces their binding into pro-inflammatory responses. Upon ligand binding, uses TIRAP and MYD88 as adapters to transduce the signal ultimately leading to the induction or inflammatory cytokines IL6, IL8 and TNFalpha through activation of NF-kappa-B 5. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key pro-inflammatory mediators 6. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons 7. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space. Participates in endothelial albumin transcytosis together with HMGB1 through the RAGE/SRC/Caveolin-1 pathway, leading to endothelial hyperpermeability 8. Mediates the loading of HMGB1 in extracellular vesicles (EVs) that shuttle HMGB1 to hepatocytes by transferrin-mediated endocytosis and subsequently promote hepatocyte pyroptosis by activating the NLRP3 inflammasome 9. Promotes also extracellular hypomethylated DNA (CpG DNA) uptake by cells via the endosomal route to activate inflammatory responses 10, 11.... show less
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Inflammatory response
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847). [provided by RefSeq, May 2011]... show less

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