P18649 · APOE_CANLF

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.

132350100150200250300
TypeIDPosition(s)Description
Binding site168-171heparin (UniProtKB | ChEBI)
Binding site235-242heparin (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentchylomicron
Cellular Componentextracellular exosome
Cellular Componentextracellular matrix
Cellular Componentextracellular space
Cellular Componentextracellular vesicle
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 Functioncholesterol transfer activity
Molecular Functionheparan sulfate proteoglycan binding
Molecular Functionheparin binding
Molecular Functionidentical protein binding
Molecular Functionlow-density lipoprotein particle receptor binding
Molecular Functionphosphatidylcholine-sterol O-acyltransferase activator activity
Molecular Functionphospholipid binding
Biological Processacylglycerol homeostasis
Biological Processcholesterol efflux
Biological Processcholesterol metabolic process
Biological Processchylomicron remnant clearance
Biological Processhigh-density lipoprotein particle assembly
Biological Processintermediate-density lipoprotein particle clearance
Biological Processlipoprotein biosynthetic process
Biological Processmelanosome organization
Biological Processnegative regulation of amyloid fibril formation
Biological Processphospholipid efflux
Biological Processpositive regulation of amyloid-beta clearance
Biological Processtriglyceride-rich lipoprotein particle clearance
Biological Processvery-low-density lipoprotein particle clearance

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Apolipoprotein E
  • Short names
    Apo-E

Gene names

    • Name
      APOE

Organism names

Accessions

  • Primary accession
    P18649
  • Secondary accessions
    • F1PJ74

Proteomes

Organism-specific databases

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_000019163619-323Apolipoprotein E
Modified residue149Methionine sulfoxide
Modified residue153Phosphoserine

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

Proteomic 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.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for repeat, region.

Type
IDPosition(s)Description
Repeat86-1071
Region86-2618 X 22 AA approximate tandem repeats
Repeat108-1292
Repeat130-1513
Repeat152-1734
Region164-174LDL and other lipoprotein receptors binding
Repeat174-1955
Repeat196-2176
Region216-296Lipid-binding and lipoprotein association
Repeat218-2397
Repeat240-2618
Region272-323Homooligomerization
Region284-296Specificity 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
    323
  • Mass (Da)
    37,224
  • Last updated
    2019-12-11 v3
  • MD5 Checksum
    323BCE55DD828081914B5957A1F6ADC1
MKVLWAALVVTLLAGCWADVQPEPELERELEPKVQQELEPEAGWQTGQPWEAALARFWDYLRWVQTLSDQVQEGVLNTQVTQELTALMDETMKEVKAYKAELDEQLGPMTSETQARVAKELQAAQARLRSDMEDVRNRLTQYRGELQAMLGQSSEELRARFASHMRKLRKRVLRDAEDLQRRLAVYKAGVREGAERSVSSIRERLWPLLEQARERNAKVGALATQPLLERADALGQQLRGQLEEMSSRARGHLEEMREQIQEVRVKMEEQADQIRQKAEAFQARLKSWFEPLLEDMQRQWDGLVEKVQAAVATIPTSKPVEEP

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict130in Ref. 3
Sequence conflict234in Ref. 3

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AAEX03000895
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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