P18287 · APOE_RABIT

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 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.

Features

Showing features for binding site.

131120406080100120140160180200220240260280300
TypeIDPosition(s)Description
Binding site155-158heparin (UniProtKB | ChEBI)
Binding site222-229heparin (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchylomicron
Cellular Componentextracellular exosome
Cellular Componentextracellular matrix
Cellular Componenthigh-density lipoprotein particle
Cellular Componentintermediate-density lipoprotein particle
Cellular Componentlow-density lipoprotein particle
Cellular Componentmultivesicular body, internal vesicle
Cellular Componentvery-low-density lipoprotein particle
Molecular Functionamyloid-beta binding
Molecular Functionheparan sulfate proteoglycan binding
Molecular Functionheparin binding
Molecular Functionidentical protein binding
Molecular Functionlipid binding
Molecular Functionlow-density lipoprotein particle receptor binding
Molecular Functionpeptide binding
Molecular Functionprotein homodimerization activity
Molecular Functionvery-low-density lipoprotein particle receptor binding
Biological Processcholesterol catabolic process
Biological Processcholesterol efflux
Biological Processchylomicron remnant clearance
Biological Processhigh-density lipoprotein particle assembly
Biological Processintermediate-density lipoprotein particle clearance
Biological Processlipoprotein biosynthetic process
Biological Processlipoprotein catabolic process
Biological Processmelanosome organization
Biological Processnegative regulation of neuron apoptotic process
Biological Processregulation of amyloid-beta clearance
Biological Processtriglyceride-rich lipoprotein particle clearance
Biological Processvery-low-density lipoprotein particle 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 > Glires > Lagomorpha > Leporidae > Oryctolagus

Accessions

  • Primary accession
    P18287

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, glycosylation.

TypeIDPosition(s)Description
Signal1-18
ChainPRO_000000199519-311Apolipoprotein E
Modified residue136Methionine sulfoxide
Modified residue140Phosphoserine
Glycosylation205O-linked (GalNAc...) threonine

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 databases

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
Repeat74-951
Region74-2488 X 22 AA approximate tandem repeats
Repeat96-1162
Repeat117-1383
Repeat139-1604
Region151-161LDL and other lipoprotein receptors binding
Repeat161-1825
Repeat183-2046
Region203-283Lipid-binding and lipoprotein association
Repeat205-2267
Repeat227-2488
Region259-311Homooligomerization
Region271-283Specificity for association with VLDL

Sequence similarities

Belongs to the apolipoprotein A1/A4/E family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    311
  • Mass (Da)
    35,497
  • Last updated
    1990-11-01 v1
  • Checksum
    3E1566BC1AAE2655
MKVWWAVLAAAILAGCRAQTEQEVEVPEQARWKAGQPWELALGRFWDYLRWVQSLSDQVQEELLSSQVTQELTMLMEETMKEVKAYKSELEEQLSPMAQEHRARLSKELQVAGALEADMEDVCNRLAQYRGEAQAMLGQSTEELARAFSSHLRKLRKRLLRDAEDLQKRMAVYGAGAREGAERGVSAVRERLGSRLERGRLRVATVGTLAGRPLRERAQAWGERLRGHLEEVGSRARDRLNEVREQVEEVRVKVEEQAPQMRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKLQAAMPSKAPAAAPIENQ

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M36603
EMBL· GenBank· DDBJ
AAA31164.1
EMBL· GenBank· DDBJ
mRNA

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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