P0DUY6 · APOE_DINBR
- ProteinApolipoprotein E
- GeneAPOE
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids300 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
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. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. 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). 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. 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. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. 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. By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis. 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. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | chylomicron | |
Cellular Component | extracellular exosome | |
Cellular Component | high-density lipoprotein particle | |
Cellular Component | intermediate-density lipoprotein particle | |
Cellular Component | multivesicular body, internal vesicle | |
Cellular Component | very-low-density lipoprotein particle | |
Molecular Function | amyloid-beta binding | |
Molecular Function | heparin binding | |
Molecular Function | lipid binding | |
Molecular Function | low-density lipoprotein particle receptor binding | |
Molecular Function | very-low-density lipoprotein particle receptor binding | |
Biological Process | cholesterol catabolic process | |
Biological Process | lipid transport | |
Biological Process | lipoprotein catabolic process | |
Biological Process | melanosome organization | |
Biological Process | negative regulation of neuron apoptotic process | |
Biological Process | positive regulation of nitric-oxide synthase activity | |
Biological Process | regulation of amyloid-beta clearance |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameApolipoprotein E
- Short namesApo-E
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Hystricomorpha > Dinomyidae > Dinomys
Accessions
- Primary accessionP0DUY6
Subcellular Location
UniProt Annotation
GO Annotation
Note: In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins. Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner. Lipidation induces the release from the extracellular matrix. Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-18 | |||||
Sequence: MKVLWAVLVVTLLAGCQA | ||||||
Chain | PRO_0000454010 | 19-300 | Apolipoprotein E | |||
Sequence: DVEPELEAQEPAVWQNGQPWELALGRFWDYLRWVQTLSDQVQEELLSSQVTQELTVLMEDTMKEVKAYKSELEQELAPMAEETKARLSKELKAAQARLGADMEEVRNRLSQYRGEVQSMLGHSAEELRARLATHLRKLRKRLLRDAEDLQKRLAVYKAGASEGAERSVSAIRERLGSLVEQGRLRTAALTSQPLQERAQAWGERLRGRLEEVGSKARDRLDEVREQMEEVRLKVEEQAEAFQARLKGWFEPMMEDIRRQWADLIEKMQAAVGTSTPAPTQKP | ||||||
Modified residue | 137 | Methionine sulfoxide | ||||
Sequence: M | ||||||
Modified residue | 141 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma. The extent of glycosylation and sialylation are tissue and context specific.
Glycated in plasma VLDL.
Phosphorylated by FAM20C in the extracellular medium.
Keywords
- PTM
Interaction
Subunit
Homotetramer. May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear. May interact with MAPT. May interact with MAP2. In the cerebrospinal fluid, interacts with secreted SORL1. Interacts with PMEL; this allows the loading of PMEL luminal fragment on ILVs to induce fibril nucleation.
Family & Domains
Features
Showing features for region, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 74-246 | 8 X 22 AA approximate tandem repeats | ||||
Sequence: VLMEDTMKEVKAYKSELEQELAPMAEETKARLSKELKAAQARLGADMEEVRNRLSQYRGEVQSMLGHSAEELRARLATHLRKLRKRLLRDAEDLQKRLAVYKAGASEGAERSVSAIRERLGSLVEQGRLRTAALTSQPLQERAQAWGERLRGRLEEVGSKARDRLDEVREQME | ||||||
Repeat | 75-95 | 1 | ||||
Sequence: LMEDTMKEVKAYKSELEQELA | ||||||
Repeat | 96-117 | 2 | ||||
Sequence: PMAEETKARLSKELKAAQARLG | ||||||
Repeat | 118-139 | 3 | ||||
Sequence: ADMEEVRNRLSQYRGEVQSMLG | ||||||
Repeat | 140-161 | 4 | ||||
Sequence: HSAEELRARLATHLRKLRKRLL | ||||||
Region | 152-162 | LDL and other lipoprotein receptors binding | ||||
Sequence: HLRKLRKRLLR | ||||||
Repeat | 162-183 | 5 | ||||
Sequence: RDAEDLQKRLAVYKAGASEGAE | ||||||
Repeat | 184-205 | 6 | ||||
Sequence: RSVSAIRERLGSLVEQGRLRTA | ||||||
Region | 204-274 | Lipid-binding and lipoprotein association | ||||
Sequence: TAALTSQPLQERAQAWGERLRGRLEEVGSKARDRLDEVREQMEEVRLKVEEQAEAFQARLKGWFEPMMEDI | ||||||
Repeat | 206-224 | 7 | ||||
Sequence: ALTSQPLQERAQAWGERLR | ||||||
Repeat | 225-243 | 8 | ||||
Sequence: GRLEEVGSKARDRLDEVRE | ||||||
Region | 262-274 | Specificity for association with VLDL | ||||
Sequence: RLKGWFEPMMEDI |
Sequence similarities
Belongs to the apolipoprotein A1/A4/E family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length300
- Mass (Da)34,333
- Last updated2022-02-23 v1
- Checksum848B2E2274531117