General Information:

Id: 7,255 (click here to show other Interactions for entry)
Diseases: Alzheimer disease - [OMIM]
Reference: Phillips MC(2014) Apolipoprotein E isoforms and lipoprotein metabolism IUBMB Life 66: 616-623 [PMID: 25328986]

Interaction Information:

Comment APOE4: Apolipoprotein (apo) E is a 299-residue protein which functions as a key regulator of plasma lipid levels. Human apoE exists as three common isoforms (APOE2, APOE3, APOE4) and the parent form, apoE3, operates optimally in promoting clearance of triglyceride (TG)-rich lipoproteins and is associated with normal plasma lipid levels. ApoE4 which differs from apoE3 by the single amino acid substitution Cys112Arg is also associated with dyslipidemia although binding of this isoform to the LDLR is unaffected. The amino acid substitution affects the organization and stability of both the N-terminal helix bundle domain and separately folded C-terminal domain so that apoE4 has enhanced lipid binding ability. As a consequence, apoE4 binds better than apoE3 to the surface of very low density lipoprotein (VLDL) particles and impairs their lipolytic processing in the circulation so that apoE4 is associated with a more pro-atherogenic lipoprotein-cholesterol distribution (higher VLDL-cholesterol / high density lipoprotein-cholesterol ratio). ApoE3 contains cysteine (Cys) at position 112 and Arg at position at 158, whereas apoE2 and apoE4 contains Cys and Arg, respectively, at both sites. ApoE3 and apoE4 bind to the LDLR with similarly high affinity but the binding of apoE2 is some two orders of magnitude weaker.
Formal Description
Interaction-ID: 71388

gene/protein mutant

APOE (isoform E4)

affects_activity of

Binding of APOE4 to the LDLR is unaffected