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Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit
Abstract
Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3' untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.
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Humans express three primary apoE isoforms that vary at only two of the 299 amino acids; mice express one form of apoE, the same as apoE4 at residues Arg112/Arg158, although homology between mouse and human apoE is only 70%.
“While humans express three primary isoforms that vary at only two of the 299 amino acids, mice express one form of apoE, the same as apoE4 at residues Arg112/Arg158, although the homology between m- and h-apoE is only 70% [118].”
From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [118]
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Piedrahita, J. A., Zhang, S. H., Hagaman, J. R., Oliver, P. M., & Maeda, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4471 · Cited by 944
Apolipoprotein E: Structure-Function Relationships
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A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward
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Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides
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Neuroinflammation‐induced acceleration of amyloid deposition in the APPV717F transgenic mouse
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Metadata
- Authors
- Rajavashisth, T. B., Kaptein, J. S., Reue, K. L., & Lusis, A. J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1985-12
- Volume
- 82
- Issue
- 23
- Pages
- 8085-8089
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 65
- References
- 3
- Language
- en
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