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Identification
HMDB Protein ID HMDBP01986
Secondary Accession Numbers
  • 7424
Name Apolipoprotein E
Synonyms
  1. Apo-E
Gene Name APOE
Protein Type Enzyme
Biological Properties
General Function Involved in lipid binding
Specific Function Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues
Pathways Not Available
Reactions Not Available
GO Classification
Component
extracellular region
Function
binding
lipid binding
Process
metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
establishment of localization
transport
lipoprotein metabolic process
lipid transport
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location Chromosome:1
Locus 19q13.2
SNPs APOE
Gene Sequence
>954 bp
ATGAAGGTTCTGTGGGCTGCGTTGCTGGTCACATTCCTGGCAGGATGCCAGGCCAAGGTG
GAGCAAGCGGTGGAGACAGAGCCGGAGCCCGAGCTGCGCCAGCAGACCGAGTGGCAGAGC
GGCCAGCGCTGGGAACTGGCACTGGGTCGCTTTTGGGATTACCTGCGCTGGGTGCAGACA
CTGTCTGAGCAGGTGCAGGAGGAGCTGCTCAGCTCCCAAGTCACCCAAGAACTGAGGGCG
CTGATGGACGAGACCATGAAGGAGTTGAAGGCCTACAAATCGGAACTGGAGGAACAACTG
ACCCCGGTAGCGGAGGAGACGCGGGCACGGCTGTCCAAGGAGCTGCAGACGGCGCAGGCC
CGGCTGGGCGCGGACATGGAGGACGTGTGCGGCCGCCTGGTGCAGTACCGCGGCGAGGTG
CAGGCCATGCTCGGCCAGAGCACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCTGCGC
AAGCTGCGTAAGCGGCTCCTCCGCGATCCCGATGACCTGCAGAAGCGCCTGGCAGTGTAC
CAGGCCGGGGCCCGCGAGGGCGCCGAGCGCGGCCTCAGCGCCATCCGCGAGCGCCTGGGG
CCCCTGGTGGAACAGGGCCGCGTGCGGGCCGCCACTGTGGGCTCCCTGGCCGGCCAGCCG
CTACAGGAGCGGGCCCAGGCCTGGGGCGAGCGGCTGCGCGCGCGGATGGAGGAGATGGGC
AGTCGGACCCGCGACCGCCTGGACGAGGTGAAGGAGCAGGTGGCGGAGGTGCGCGCCAAG
CTGGAGGAGCAGGCCCAGCAGATACGCCTGCAGGCCGAGGCCTTCCAGGCCCGCCTCAAG
AGCTGGTTCGAGCCCCTGGTGGAAGACATGCAGCGCCAGTGGGCCGGGCTGGTGGAGAAG
GTGCAGGCTGCCGTGGGCACCAGCGCCGCCCCTGTGCCCAGCGACAATCACTGA
Protein Properties
Number of Residues 317
Molecular Weight 36153.8
Theoretical pI 5.42
Pfam Domain Function
Signals
  • 1-18
Transmembrane Regions
  • None
Protein Sequence
>Apolipoprotein E
MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQT
LSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQA
RLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVY
QAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMG
SRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEK
VQAAVGTSAAPVPSDNH
GenBank ID Protein 178849
UniProtKB/Swiss-Prot ID P02649
UniProtKB/Swiss-Prot Entry Name APOE_HUMAN
PDB IDs
GenBank Gene ID M12529
GeneCard ID APOE
GenAtlas ID APOE
HGNC ID HGNC:613
References
General References
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  3. Morabia A, Cayanis E, Costanza MC, Ross BM, Flaherty MS, Alvin GB, Das K, Gilliam TC: Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors. Hum Mol Genet. 2003 Nov 1;12(21):2733-43. Epub 2003 Sep 9. [PubMed:12966036 ]
  4. Nilsson J, Ruetschi U, Halim A, Hesse C, Carlsohn E, Brinkmalm G, Larson G: Enrichment of glycopeptides for glycan structure and attachment site identification. Nat Methods. 2009 Nov;6(11):809-11. doi: 10.1038/nmeth.1392. Epub 2009 Oct 18. [PubMed:19838169 ]
  5. Zhou W, Ross MM, Tessitore A, Ornstein D, Vanmeter A, Liotta LA, Petricoin EF 3rd: An initial characterization of the serum phosphoproteome. J Proteome Res. 2009 Dec;8(12):5523-31. doi: 10.1021/pr900603n. [PubMed:19824718 ]
  6. Freitas EM, Zhang WJ, Lalonde JP, Tay GK, Gaudieri S, Ashworth LK, Van Bockxmeer FM, Dawkins RL: Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1. DNA Seq. 1998;9(2):89-100. [PubMed:10520737 ]
  7. Zannis VI, McPherson J, Goldberger G, Karathanasis SK, Breslow JL: Synthesis, intracellular processing, and signal peptide of human apolipoprotein E. J Biol Chem. 1984 May 10;259(9):5495-9. [PubMed:6325438 ]
  8. McLean JW, Elshourbagy NA, Chang DJ, Mahley RW, Taylor JM: Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing of a new variant. J Biol Chem. 1984 May 25;259(10):6498-504. [PubMed:6327682 ]
  9. Paik YK, Chang DJ, Reardon CA, Davies GE, Mahley RW, Taylor JM: Nucleotide sequence and structure of the human apolipoprotein E gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3445-9. [PubMed:2987927 ]
  10. Emi M, Wu LL, Robertson MA, Myers RL, Hegele RA, Williams RR, White R, Lalouel JM: Genotyping and sequence analysis of apolipoprotein E isoforms. Genomics. 1988 Nov;3(4):373-9. [PubMed:3243553 ]
  11. Nickerson DA, Taylor SL, Fullerton SM, Weiss KM, Clark AG, Stengard JH, Salomaa V, Boerwinkle E, Sing CF: Sequence diversity and large-scale typing of SNPs in the human apolipoprotein E gene. Genome Res. 2000 Oct;10(10):1532-45. [PubMed:11042151 ]
  12. Breslow JL, McPherson J, Nussbaum AL, Williams HW, Lofquist-Kahl F, Karathanasis SK, Zannis VI: Identification and DNA sequence of a human apolipoprotein E cDNA clone. J Biol Chem. 1982 Dec 25;257(24):14639-41. [PubMed:6897404 ]
  13. Rall SC Jr, Weisgraber KH, Mahley RW: Human apolipoprotein E. The complete amino acid sequence. J Biol Chem. 1982 Apr 25;257(8):4171-8. [PubMed:7068630 ]
  14. Mahley RW: Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622-30. [PubMed:3283935 ]
  15. Cardin AD, Hirose N, Blankenship DT, Jackson RL, Harmony JA, Sparrow DA, Sparrow JT: Binding of a high reactive heparin to human apolipoprotein E: identification of two heparin-binding domains. Biochem Biophys Res Commun. 1986 Jan 29;134(2):783-9. [PubMed:3947350 ]
  16. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993 Aug 13;261(5123):921-3. [PubMed:8346443 ]
  17. Shuvaev VV, Fujii J, Kawasaki Y, Itoh H, Hamaoka R, Barbier A, Ziegler O, Siest G, Taniguchi N: Glycation of apolipoprotein E impairs its binding to heparin: identification of the major glycation site. Biochim Biophys Acta. 1999 Aug 30;1454(3):296-308. [PubMed:10452964 ]
  18. Wilson C, Wardell MR, Weisgraber KH, Mahley RW, Agard DA: Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E. Science. 1991 Jun 28;252(5014):1817-22. [PubMed:2063194 ]
  19. Dong LM, Parkin S, Trakhanov SD, Rupp B, Simmons T, Arnold KS, Newhouse YM, Innerarity TL, Weisgraber KH: Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia. Nat Struct Biol. 1996 Aug;3(8):718-22. [PubMed:8756331 ]
  20. Segelke BW, Forstner M, Knapp M, Trakhanov SD, Parkin S, Newhouse YM, Bellamy HD, Weisgraber KH, Rupp B: Conformational flexibility in the apolipoprotein E amino-terminal domain structure determined from three new crystal forms: implications for lipid binding. Protein Sci. 2000 May;9(5):886-97. [PubMed:10850798 ]
  21. de Knijff P, van den Maagdenberg AM, Frants RR, Havekes LM: Genetic heterogeneity of apolipoprotein E and its influence on plasma lipid and lipoprotein levels. Hum Mutat. 1994;4(3):178-94. [PubMed:7833947 ]
  22. Maeda H, Nakamura H, Kobori S, Okada M, Niki H, Ogura T, Hiraga S: Molecular cloning of a human apolipoprotein E variant: E5 (Glu3----Lys3). J Biochem. 1989 Apr;105(4):491-3. [PubMed:2760009 ]
  23. Wardell MR, Weisgraber KH, Havekes LM, Rall SC Jr: Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a tandem repeat of residues 121-127. J Biol Chem. 1989 Dec 15;264(35):21205-10. [PubMed:2556398 ]
  24. Lohse P, Mann WA, Stein EA, Brewer HB Jr: Apolipoprotein E-4Philadelphia (Glu13----Lys,Arg145----Cys). Homozygosity for two rare point mutations in the apolipoprotein E gene combined with severe type III hyperlipoproteinemia. J Biol Chem. 1991 Jun 5;266(16):10479-84. [PubMed:1674745 ]
  25. van den Maagdenberg AM, Weng W, de Bruijn IH, de Knijff P, Funke H, Smelt AH, Gevers Leuven JA, van't Hooft FM, Assmann G, Hofker MH, et al.: Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: no cosegregation with severe hyperlipidemia. Am J Hum Genet. 1993 May;52(5):937-46. [PubMed:8488843 ]
  26. Richard P, Thomas G, de Zulueta MP, De Gennes JL, Thomas M, Cassaigne A, Bereziat G, Iron A: Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA. Clin Chem. 1994 Jan;40(1):24-9. [PubMed:8287539 ]
  27. Oikawa S, Matsunaga A, Saito T, Sato H, Seki T, Hoshi K, Hayasaka K, Kotake H, Midorikawa H, Sekikawa A, Hara S, Abe K, Toyota T, Jingami H, Nakamura H, Sasaki J: Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy. J Am Soc Nephrol. 1997 May;8(5):820-3. [PubMed:9176854 ]
  28. Kang AK, Jenkins DJ, Wolever TM, Huff MW, Maguire GF, Connelly PW, Hegele RA: Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease. Mutat Res. 1997 Sep;382(1-2):57-65. [PubMed:9360638 ]
  29. Matsunaga A, Sasaki J, Komatsu T, Kanatsu K, Tsuji E, Moriyama K, Koga T, Arakawa K, Oikawa S, Saito T, Kita T, Doi T: A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy. Kidney Int. 1999 Aug;56(2):421-7. [PubMed:10432380 ]
  30. Nguyen TT, Kruckeberg KE, O'Brien JF, Ji ZS, Karnes PS, Crotty TB, Hay ID, Mahley RW, O'Brien T: Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)]. J Clin Endocrinol Metab. 2000 Nov;85(11):4354-8. [PubMed:11095479 ]
  31. Miserez AR, Scharnagl H, Muller PY, Mirsaidi R, Stahelin HB, Monsch A, Marz W, Hoffmann MM: Apolipoprotein E3Basel: new insights into a highly conserved protein region. Eur J Clin Invest. 2003 Aug;33(8):677-85. [PubMed:12864777 ]
  32. Faivre L, Saugier-Veber P, Pais de Barros JP, Verges B, Couret B, Lorcerie B, Thauvin C, Charbonnier F, Huet F, Gambert P, Frebourg T, Duvillard L: Variable expressivity of the clinical and biochemical phenotype associated with the apolipoprotein E p.Leu149del mutation. Eur J Hum Genet. 2005 Nov;13(11):1186-91. [PubMed:16094309 ]
  33. Rovin BH, Roncone D, McKinley A, Nadasdy T, Korbet SM, Schwartz MM: APOE Kyoto mutation in European Americans with lipoprotein glomerulopathy. N Engl J Med. 2007 Dec 13;357(24):2522-4. [PubMed:18077821 ]