P0DTR8 · APOE_THEGE

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.

TypeIDPosition(s)Description
Binding site162-165heparin (UniProtKB | ChEBI)
Binding site229-236heparin (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchylomicron
Cellular Componentextracellular exosome
Cellular Componenthigh-density lipoprotein particle
Cellular Componentintermediate-density lipoprotein particle
Cellular Componentmultivesicular body, internal vesicle
Cellular Componentvery-low-density lipoprotein particle
Molecular Functionamyloid-beta binding
Molecular Functionheparin binding
Molecular Functionlipid binding
Molecular Functionlow-density lipoprotein particle receptor binding
Molecular Functionvery-low-density lipoprotein particle receptor binding
Biological Processcholesterol catabolic process
Biological Processlipid transport
Biological Processlipoprotein catabolic process
Biological Processmelanosome organization
Biological Processnegative regulation of neuron apoptotic process
Biological Processregulation of amyloid-beta clearance

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Apolipoprotein E
  • Short names
    Apo-E

Gene names

    • Name
      APOE

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Theropithecus

Accessions

  • Primary accession
    P0DTR8

Proteomes

Subcellular Location

Secreted
Extracellular vesicle
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

PTM/Processing

Features

Showing features for signal, chain, modified residue.

TypeIDPosition(s)Description
Signal1-18
ChainPRO_000044876319-317Apolipoprotein E
Modified residue143Methionine sulfoxide
Modified residue147Phosphoserine

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

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.

Structure

Family & Domains

Features

Showing features for repeat, region.

TypeIDPosition(s)Description
Repeat80-1011
Region80-2558 X 22 AA approximate tandem repeats
Repeat102-1232
Repeat124-1453
Repeat146-1674
Region158-168LDL and other lipoprotein receptors binding
Repeat168-1895
Repeat190-2116
Region210-290Lipid-binding and lipoprotein association
Repeat212-2337
Repeat234-2558
Region266-317Homooligomerization
Region278-290Specificity for association with VLDL

Sequence similarities

Belongs to the apolipoprotein A1/A4/E family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    317
  • Mass (Da)
    36,035
  • Last updated
    2019-12-11 v1
  • Checksum
    97C4AC3AAF8398FF
MKVLWAALLVTFLAGCQAKVEQPVEPETEPELRQQAEWQSGQPWELALGRFWDYLRWVQTLSEQVQEELLSPQVTQELTTLMDETMKELKAYKSELEEQLSPVAEETRARLSKELQAAQARLGADMEDVRSRLVQYRSELQAMLGQSTEELRARLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGVSAIRERLGPLVEQGRVRAATVGSLASQPLQERAQALGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQISLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGASTAPVPSDNH

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
CM009950
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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