Q9GLC0 · APOE_TUPGL

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.

131320406080100120140160180200220240260280300
TypeIDPosition(s)Description
Binding site158-161heparin (UniProtKB | ChEBI)
Binding site225-232heparin (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchylomicron
Cellular Componentextracellular exosome
Cellular Componentextracellular matrix
Cellular Componentextracellular space
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 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 amyloid fibril formation
Biological Processnegative regulation of neuron apoptotic process
Biological Processpositive regulation of amyloid-beta clearance
Biological Processpositive regulation of nitric-oxide synthase activity
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

Accessions

  • Primary accession
    Q9GLC0

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_000000199819-313Apolipoprotein E
Modified residue139Methionine sulfoxide
Modified residue143Phosphoserine

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.

Type
IDPosition(s)Description
Repeat76-971
Region76-2518 X 22 AA approximate tandem repeats
Repeat98-1192
Repeat120-1413
Repeat142-1634
Region154-164LDL and other lipoprotein receptors binding
Repeat164-1855
Repeat186-2076
Region206-286Lipid-binding and lipoprotein association
Repeat208-2297
Repeat230-2518
Region262-313Homooligomerization
Region274-286Specificity 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
    313
  • Mass (Da)
    35,923
  • Last updated
    2001-03-01 v1
  • Checksum
    015D4D91F1D905BA
MKVLWAVLAFAFLTGCRADVEPQLEPEVREPPKWQAGQPWELALGRFWDYLRWVQTLSDQVQEELLSSQVTQELTVLMEETMKEVKAYKAELEEQLGPMKEETQARLSKELQAAQARLGADMEDVRTRLAQYRSEVHTMLGQSTEELRARLSSHLRKMRKRLLRDAEDLQKRLAVYRAGVQEGAERGVSAIRERLGPLMEQGRLRANTVSALAVQPLQERAQAWGERLRGRLQEVGSQARDRLDEVREQVEEVRAKVEEQATQMRLQAEAFQARLQSWFEPLVKDVQRQWAELVEKVQAAVGTSAAPVSSENH

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF303830
EMBL· GenBank· DDBJ
AAG21401.1
EMBL· GenBank· DDBJ
mRNA

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Disclaimer

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