P0DUZ9 · APOE_THRSW

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 site156-159heparin (UniProtKB | ChEBI)
Binding site219-226heparin (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 Processpositive regulation of nitric-oxide synthase activity
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

Accessions

  • Primary accession
    P0DUZ9

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.

Type
IDPosition(s)Description
Signal1-18
ChainPRO_000045402319-299Apolipoprotein E
Modified residue137Methionine sulfoxide
Modified residue141Phosphoserine

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

3D structure databases

Family & Domains

Features

Showing features for repeat, region.

Type
IDPosition(s)Description
Repeat74-951
Region74-2458 X 22 AA approximate tandem repeats
Repeat96-1172
Repeat118-1393
Repeat140-1614
Region152-162LDL and other lipoprotein receptors binding
Repeat162-1835
Repeat184-2056
Region204-273Lipid-binding and lipoprotein association
Repeat224-2458
Region261-273Specificity 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
    299
  • Mass (Da)
    34,223
  • Last updated
    2022-02-23 v1
  • Checksum
    49FD3B35EAB76E1E
MKVLWALLVVTILAGCRAEVQPELEVQAPAGWQSGQPWELALGRFWDYLRWVQTLSDQVQEELLNSQVTQELTVLMEDTMKEVKAYKSELEQELGPMAEDTKARLSKELQAAQARLGADMEEVRNRLAQYRGEMQAMLGQSAEELRARLASHLRKLRKRLLRDAEDLQKRLAVYRAGAQEGAERGVSAIRERLGSLVEQSRLRAALTSQPLHERAQAWGERLRGRLEEVGGQARDRLDEVREQMQEVRAKMEEQAEAFQARLKGWFEPLVEDMRRQWSDLVEKVQVAVRASTAAPSENH

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
PVIC010012398
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Similar Proteins

Disclaimer

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