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APOE
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PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
Hippocampal formation Amygdala Basal ganglia Midbrain Spinal cord Cerebral cortex Cerebellum Hypothalamus Choroid plexus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Rectum Duodenum Colon Small intestine Liver Gallbladder Pancreas Kidney Urinary bladder Testis Epididymis Prostate Seminal vesicle Vagina Breast Cervix Endometrium Fallopian tube Ovary Placenta Heart muscle Skeletal muscle Smooth muscle Adipose tissue Skin Bone marrow Tonsil Thymus Appendix Lymph node Spleen
APOE INFORMATION
Proteini

Full gene name according to HGNC.

Apolipoprotein E
Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

APOE (AD2)
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

Cancer-related genes
Candidate cardiovascular disease genes
Disease related genes
Human disease related genes
Metabolic proteins
Plasma proteins
Protein evidence Evidence at protein level (all genes)
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

4
Protein interactions Interacting with 5 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.
Distinct plasma positivity. Cytoplasmic expression in hepatocytes, renal tubules, Leydig cells, adrenal gland and subset of neurons.
Subcellular locationi

Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.

Localized to the Vesicles
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
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.

Secreted to blood
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.

Group enriched (Adrenal gland, Brain, Liver)
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.

Liver - Oxidoreductase activity (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

Low human brain regional specificity
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.

Astrocytes - Mixed function (mainly)
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 enhanced (Muller glia cells, Hepatocytes, Proximal tubular cells, Hofbauer cells, Peritubular cells, Melanocytes, Leydig cells)
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.

Macrophages - Innate immune response (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 in 8 tissues
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 APOE is a prognostic marker in Liver hepatocellular carcinoma
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.

Cancer enhanced (Liver Hepatocellular 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.

Leukemia - Hemostasis (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 (Liver cancer, Rhabdoid)
PROTEINS IN BLOOD
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.

Secreted to blood
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.

Yes
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
Not available
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids 1, 2, 3. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance 4, 5, 6, 7, 8, 9, 10. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma 11, 12, 13. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) 14, 15. It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells 27, 28, 29, 30. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes 31, 32, 33, 34, 35. APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues 36, 37. By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis 38, 39, 40. APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis 41, 42, 43. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues 44, 45. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes 46. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting 47, 48. APOE is also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). Binds to the immune cell receptor LILRB4 49. APOE may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP 50.... show less
Molecular function (UniProt)i

Keywords assigned by UniProt to proteins due to their particular molecular function.

Heparin-binding
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Cholesterol metabolism, Host-virus interaction, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

Lipid-binding
Gene summary (Entrez)i

Useful information about the gene from Entrez

The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]... show less

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