Nucleotide sequence and structure of the human apolipoprotein E gene.
Open accessAbstract
The gene for human apolipoprotein E (apo-E) was selected from a library of cloned genomic DNA by screening with a specific cDNA hybridization probe, and its structure was characterized. The complete nucleotide sequence of the gene as well as 856 nucleotides of the 5' flanking region and 629 nucleotides of the 3' flanking region were determined. Analysis of the sequence showed that the mRNA-encoding region of the apo-E gene consists of four exons separated by three introns. In comparison to the structure of the mRNA, the introns are located in the 5' noncoding region, in the codon for glycine at position -4 of the signal peptide region, and in the codon for arginine at position +61 of the mature protein. The overall lengths of the apo-E gene and its corresponding mRNA are 3597 and 1163 nucleotides, respectively; a mature plasma protein of 299 amino acids is produced by this gene. Examination of the 5' terminus of the gene by S1 nuclease mapping shows apparent multiple transcription initiation sites. The proximal 5' flanking region contains a "TATA box" element as well as two nearby inverted repeat elements. In addition, there are four Alu family sequences associated with the apo-E gene: an Alu sequence located near each end of the gene and two Alu sequences located in the second intron. This knowledge of the structure permits a molecular approach to characterizing the regulation of the apo-E gene.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The APOE start codon is located in exon 2, and exons 2, 3, and 4 are the regions of the APOE gene encoding the expressed amino acids.
“As shown in Fig.4, the APOE start codon is located in exon 2, and exons 2, 3, and 4 are the regions of the APOE gene encoding the expressed amino acids22).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Human apolipoprotein E. The complete amino acid sequence
Rall, S. C., Weisgraber, K. H., & Mahley, R. W. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34702-1 · Cited by 741 · see citing works
Self-citationRall, S. C., Weisgraber, K. H., Innerarity, T. L., & Mahley, R. W. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.15.4696 · Cited by 345 · see citing works
Self-citationThe receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments.
Innerarity, T. L., Friedlander, E. J., Rall, S. C., Weisgraber, K. H., & Mahley, R. W. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44180-9 · Cited by 276 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 5
- Paoletti, R. & Gotto, A. M., Jr. (Raven, New York), Vol. 5, pp. 1-34.
- Elshourbagy, N. A., Liao, W. S., Mahley, R. W. & Taylor, J. M. (1985) Proc. Natl. Acad. Sci. USA 82, 203-207.
- Rall, S. C., Jr., Weisgraber, K. H., Innerarity, T. L. & Mahley, R. W. (1982) Proc. Natl. Acad. Sci. USA 79, 4696-4700.
- Breathnach, R., Benoist, C., O'Hare, K., Gannon, F. & Chambon, P. (1978) Proc. Natl. Acad. Sci. USA 75, 4853-4857.
- Karathanasis, S. K., Zannis, V. I. & Breslow, J. L. (1983) Proc. Natl. Acad. Sci. USA 80, 6147-6151.
Cited by
Sorted by citations
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · see citing works
Self-citationApolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981 · see citing works
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830 · see citing works
Low nucleotide diversity in man.
Li, W. H., & Sadler, L. A. (1991) · Genetics · doi:10.1093/genetics/129.2.513 · Cited by 501 · see citing works
Genetic and epigenetic regulation of human aging and longevity
Morris, B. J., Willcox, B. J., & Donlon, T. A. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.039 · Cited by 140 · see citing works
de Knijff, P., van den Maagdenberg, A. M., Stalenhoef, A. F., Leuven, J. A., Demacker, P. N., Kuyt, L. P., Frants, R. R., & Havekes, L. M. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115349 · Cited by 100 · see citing works
Cladaras, C., Hadzopoulou-Cladaras, M., Felber, B. K., Pavlakis, G., & Zannis, V. I. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61655-2 · Cited by 92 · see citing works
Vogel, T., Weisgraber, K. H., Zeevi, M. I., Ben-Artzi, H., Levanon, A. Z., Rall, S. C., Innerarity, T. L., Hui, D. Y., Taylor, J. M., & Kanner, D. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.24.8696 · Cited by 88 · see citing works
Self-citationWardell, M. R., Weisgraber, K. H., Havekes, L. M., & Rall, S. C. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)30067-5 · Cited by 80 · see citing works
Smit, M., de Knijff, P., van der Kooij-Meijs, E., Groenendijk, C., van den Maagdenberg, A., Gevers Leuven, J., Stalenhoef, A., Stuyt, P., Frants, R., & Havekes, L. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42759-2 · Cited by 74 · see citing works
Maloney, B., Ge, Y., Alley, G. M., & Lahiri, D. K. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04831.x · Cited by 63 · see citing works
Vogt, B. A., Vogt, L. J., Vrana, K. E., Gioia, L., Meadows, R. S., Challa, V. R., Hof, P. R., & Van Hoesen, G. W. (1998) · Experimental Neurology · doi:10.1006/exnr.1998.6852 · Cited by 64 · see citing works
Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects
Mailly, F., Xu, C., Xhignesse, M., Lussier-Cacan, S., Talmud, P., Davignon, J., Humphries, S., & Nestruck, A. (1991) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42048-6 · Cited by 36 · see citing works
Mitsumori, R., Sakaguchi, K., Shigemizu, D., Mori, T., Akiyama, S., Ozaki, K., Niida, S., & Shimoda, N. (2020) · PLOS ONE · doi:10.1371/journal.pone.0239196 · Cited by 34 · see citing works
Identification of Human Apolipoprotein E Variant Gene: Apolipoprotein E7 (Glu244,245↑Lys244,245)1
Maeda, H., Nakamura, H., Kobori, S., Okada, M., Mori, H., Niki, H., Ogura, T., & Hiraga, S. (1989) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a122618 · Cited by 29 · see citing works
FEUSSNER, G., FUNKE, H., WENG, W., ASSMANN, G., LACKNER, K. J., & ZIEGLER, R. (1992) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1992.tb01511.x · Cited by 28 · see citing works
Feussner, G., Scharnagl, H., Scherbaum, C., Acar, J., Dobmeyer, J., Lohrmann, J., Wieland, H., & März, W. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39106-9 · Cited by 21 · see citing works
Zannis, V. I., Ordovas, J. M., Cladaras, C., Cole, F. S., Forbes, G., & Schaefer, E. J. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38808-7 · Cited by 21 · see citing works
Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
Matsunaga, A., & Saito, T. (2025) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.65393 · Cited by 14 · see citing works
Scacchi, R., Gambina, G., Ferrari, G., & Corbo, R. M. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00089-1 · Cited by 14 · see citing works
Severe xanthomatosis associated with familial apolipoprotein E deficiency.
Feussner, G. (1996) · Journal of Clinical Pathology · doi:10.1136/jcp.49.12.985 · Cited by 10 · see citing works
Dijck-Brouwer, D. A. J., van Doormaal, J. J., Kema, I. P., Brugman, A. M., Kingma, A. W., & Muskiet, F. A. J. (2005) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1258/0004563054255498 · Cited by 9 · see citing works
Feussner, G., Albanese, M., & Valencia, A. (1996) · Atherosclerosis · doi:10.1016/0021-9150(96)05870-4 · Cited by 7 · see citing works
- Authors
- Paik, Y. K., Chang, D. J., Reardon, C. A., Davies, G. E., Mahley, R. W., & Taylor, J. M.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1985-05
- Volume
- 82
- Issue
- 10
- Pages
- 3445-3449
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC397792
- OpenAlex
- W2080831516
- Cited by
- 281
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 3
- FWCI
- 20.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- apolipoprotein E, gene structure, nucleotide sequence, 5'-flanking region, 3' flanking region, introns, exons, signal peptide, transcription start sites, TATA box, inverted repeats, Alu elements, gene expression regulation, mRNA
- MeSH terms
- Amino Acid Sequence, Apolipoproteins, Apolipoproteins E, Base Sequence, Endonucleases, Genes, Humans, Genetic Linkage, Repetitive Sequences, Nucleic Acid, Single-Strand Specific DNA and RNA Endonucleases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
