APOE_HUMAN
ID APOE_HUMAN Reviewed; 317 AA.
AC P02649; B2RC15; C0JYY5; Q9P2S4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 261.
DE RecName: Full=Apolipoprotein E {ECO:0000305};
DE Short=Apo-E;
DE Flags: Precursor;
GN Name=APOE {ECO:0000312|HGNC:HGNC:613};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE APOE*3).
RX PubMed=6325438; DOI=10.1016/s0021-9258(18)91039-2;
RA Zannis V.I., McPherson J., Goldberger G., Karathanasis S.K., Breslow J.L.;
RT "Synthesis, intracellular processing, and signal peptide of human
RT apolipoprotein E.";
RL J. Biol. Chem. 259:5495-5499(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS THR-117 AND PRO-170.
RX PubMed=6327682; DOI=10.1016/s0021-9258(20)82169-3;
RA McLean J.W., Elshourbagy N.A., Chang D.J., Mahley R.W., Taylor J.M.;
RT "Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing of a
RT new variant.";
RL J. Biol. Chem. 259:6498-6504(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*4), AND VARIANT AD2 ARG-130.
RX PubMed=2987927; DOI=10.1073/pnas.82.10.3445;
RA Paik Y.-K., Chang D.J., Reardon C.A., Davies G.E., Mahley R.W.,
RA Taylor J.M.;
RT "Nucleotide sequence and structure of the human apolipoprotein E gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3445-3449(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*2), AND VARIANT CYS-176.
RX PubMed=3243553; DOI=10.1016/0888-7543(88)90130-9;
RA Emi M., Wu L.L., Robertson M.A., Myers R.L., Hegele R.A., Williams R.R.,
RA White R., Lalouel J.-M.;
RT "Genotyping and sequence analysis of apolipoprotein E isoforms.";
RL Genomics 3:373-379(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3).
RX PubMed=10520737; DOI=10.3109/10425179809086433;
RA Freitas E.M., Zhang W.J., Lalonde J.P., Tay G.K., Gaudieri S.,
RA Ashworth L.K., Van Bockxmeer F.M., Dawkins R.L.;
RT "Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene:
RT PEREC1.";
RL DNA Seq. 9:89-100(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3), AND VARIANTS PRO-46;
RP ARG-130; CYS-163 AND CYS-176.
RX PubMed=11042151; DOI=10.1101/gr.146900;
RA Nickerson D.A., Taylor S.L., Fullerton S.M., Weiss K.M., Clark A.G.,
RA Stengard J.H., Salomaa V., Boerwinkle E., Sing C.F.;
RT "Sequence diversity and large-scale typing of SNPs in the human
RT apolipoprotein E gene.";
RL Genome Res. 10:1532-1545(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE APOE*3).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE APOE*3).
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE APOE*3).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-78, AND VARIANT HIS-64.
RC TISSUE=Blood;
RA Imura T., Kimura H., Kawasaki M.;
RT "A new apolipoprotein E variant (Gln46-->His).";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 99-317 (ALLELE APOE*3).
RX PubMed=6897404; DOI=10.1016/s0021-9258(18)33328-3;
RA Breslow J.L., McPherson J., Nussbaum A.L., Williams H.W., Lofquist-Kahl F.,
RA Karathanasis S.K., Zannis V.I.;
RT "Identification and DNA sequence of a human apolipoprotein E cDNA clone.";
RL J. Biol. Chem. 257:14639-14641(1982).
RN [12]
RP ERRATUM OF PUBMED:6897404.
RA Breslow J.L., McPherson J., Nussbaum A.L., Williams H.W., Lofquist-Kahl F.,
RA Karathanasis S.K., Zannis V.I.;
RL J. Biol. Chem. 258:11422-11422(1983).
RN [13]
RP PROTEIN SEQUENCE OF 19-317 (ALLELE APOE*2).
RX PubMed=7068630; DOI=10.1016/s0021-9258(18)34702-1;
RA Rall S.C. Jr., Weisgraber K.H., Mahley R.W.;
RT "Human apolipoprotein E. The complete amino acid sequence.";
RL J. Biol. Chem. 257:4171-4178(1982).
RN [14]
RP FUNCTION IN LIPOPROTEINS CONVERSION.
RX PubMed=6860692; DOI=10.1016/0005-2760(83)90047-4;
RA Marcel Y.L., Vezina C., Milne R.W.;
RT "Cholesteryl ester and apolipoprotein E transfer between human high density
RT lipoproteins and chylomicrons.";
RL Biochim. Biophys. Acta 750:411-417(1983).
RN [15]
RP HEPARIN-BINDING SITES.
RX PubMed=3947350; DOI=10.1016/s0006-291x(86)80489-2;
RA Cardin A.D., Hirose N., Blankenship D.T., Jackson R.L., Harmony J.A.K.,
RA Sparrow D.A., Sparrow J.T.;
RT "Binding of a high reactive heparin to human apolipoprotein E:
RT identification of two heparin-binding domains.";
RL Biochem. Biophys. Res. Commun. 134:783-789(1986).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=3115992; DOI=10.1016/s0021-9258(18)47945-8;
RA Pitas R.E., Boyles J.K., Lee S.H., Hui D., Weisgraber K.H.;
RT "Lipoproteins and their receptors in the central nervous system.
RT Characterization of the lipoproteins in cerebrospinal fluid and
RT identification of apolipoprotein B,E(LDL) receptors in the brain.";
RL J. Biol. Chem. 262:14352-14360(1987).
RN [17]
RP INTERACTION WITH SORL1.
RX PubMed=30448281; DOI=10.1016/j.cca.2018.11.024;
RA Yano K., Hirayama S., Misawa N., Furuta A., Ueno T., Motoi Y., Seino U.,
RA Ebinuma H., Ikeuchi T., Schneider W.J., Bujo H., Miida T.;
RT "Soluble LR11 competes with amyloid beta in binding to cerebrospinal fluid-
RT high-density lipoprotein.";
RL Clin. Chim. Acta 489:29-34(2019).
RN [18]
RP CHARACTERIZATION OF VARIANTS SER-154 AND PRO-170, AND MUTAGENESIS OF
RP SER-157; HIS-158; LYS-161; LEU-162; LEU-167 AND ARG-168.
RX PubMed=2831187; DOI=10.1016/s0021-9258(18)68957-4;
RA Lalazar A., Weisgraber K.H., Rall S.C. Jr., Giladi H., Innerarity T.L.,
RA Levanon A.Z., Boyles J.K., Amit B., Gorecki M., Mahley R.W.;
RT "Site-specific mutagenesis of human apolipoprotein E. Receptor binding
RT activity of variants with single amino acid substitutions.";
RL J. Biol. Chem. 263:3542-3545(1988).
RN [19]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT THR-212, AND MUTAGENESIS OF THR-212.
RX PubMed=2498325; DOI=10.1016/s0021-9258(18)81907-x;
RA Wernette-Hammond M.E., Lauer S.J., Corsini A., Walker D., Taylor J.M.,
RA Rall S.C. Jr.;
RT "Glycosylation of human apolipoprotein E. The carbohydrate attachment site
RT is threonine 194.";
RL J. Biol. Chem. 264:9094-9101(1989).
RN [20]
RP FUNCTION IN VLDL CLEARANCE.
RX PubMed=2762297; DOI=10.1073/pnas.86.15.5810;
RA Kowal R.C., Herz J., Goldstein J.L., Esser V., Brown M.S.;
RT "Low density lipoprotein receptor-related protein mediates uptake of
RT cholesteryl esters derived from apoprotein E-enriched lipoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5810-5814(1989).
RN [21]
RP REGION, AND CHARACTERIZATION OF VARIANT ARG-130 AND ARG-176.
RX PubMed=2280190;
RA Weisgraber K.H.;
RT "Apolipoprotein E distribution among human plasma lipoproteins: role of the
RT cysteine-arginine interchange at residue 112.";
RL J. Lipid Res. 31:1503-1511(1990).
RN [22]
RP FUNCTION IN CHYLOMICRONS CLEARANCE, AND SUBCELLULAR LOCATION.
RX PubMed=1911868; DOI=10.1016/0005-2760(91)90138-8;
RA Arnon R., Sehayek E., Vogel T., Eisenberg S.;
RT "Effects of exogenous apo E-3 and of cholesterol-enriched meals on the
RT cellular metabolism of human chylomicrons and their remnants.";
RL Biochim. Biophys. Acta 1085:336-342(1991).
RN [23]
RP FUNCTION IN VLDL AND IDL CLEARANCE.
RX PubMed=1917954; DOI=10.1016/s0021-9258(18)55263-7;
RA Sehayek E., Eisenberg S.;
RT "Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent
RT cellular metabolism of human triglyceride-rich lipoproteins through the low
RT density lipoprotein receptor pathway.";
RL J. Biol. Chem. 266:18259-18267(1991).
RN [24]
RP SUBUNIT, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=8340399; DOI=10.1016/s0021-9258(18)82318-3;
RA Westerlund J.A., Weisgraber K.H.;
RT "Discrete carboxyl-terminal segments of apolipoprotein E mediate
RT lipoprotein association and protein oligomerization.";
RL J. Biol. Chem. 268:15745-15750(1993).
RN [25]
RP INTERACTION WITH APP/A4 AMYLOID-BETA PEPTIDE, AND CHARACTERIZATION OF
RP VARIANT AD2 ARG-130.
RX PubMed=8367470; DOI=10.1073/pnas.90.17.8098;
RA Strittmatter W.J., Weisgraber K.H., Huang D.Y., Dong L.M., Salvesen G.S.,
RA Pericak-Vance M., Schmechel D., Saunders A.M., Goldgaber D., Roses A.D.;
RT "Binding of human apolipoprotein E to synthetic amyloid beta peptide:
RT isoform-specific effects and implications for late-onset Alzheimer
RT disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:8098-8102(1993).
RN [26]
RP INTERACTION WITH MAP2, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX PubMed=7891887; DOI=10.1016/0304-3940(94)90204-6;
RA Huang D.Y., Goedert M., Jakes R., Weisgraber K.H., Garner C.C.,
RA Saunders A.M., Pericak-Vance M.A., Schmechel D.E., Roses A.D.,
RA Strittmatter W.J.;
RT "Isoform-specific interactions of apolipoprotein E with the microtubule-
RT associated protein MAP2c: implications for Alzheimer's disease.";
RL Neurosci. Lett. 182:55-58(1994).
RN [27]
RP INTERACTION WITH MAPT, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX PubMed=7972031; DOI=10.1073/pnas.91.23.11183;
RA Strittmatter W.J., Saunders A.M., Goedert M., Weisgraber K.H., Dong L.M.,
RA Jakes R., Huang D.Y., Pericak-Vance M., Schmechel D., Roses A.D.;
RT "Isoform-specific interactions of apolipoprotein E with microtubule-
RT associated protein tau: implications for Alzheimer disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:11183-11186(1994).
RN [28]
RP FUNCTION, AND LRP2-BINDING.
RX PubMed=7768901; DOI=10.1074/jbc.270.22.13070;
RA Kounnas M.Z., Loukinova E.B., Stefansson S., Harmony J.A.K., Brewer B.H.,
RA Strickland D.K., Argraves W.S.;
RT "Identification of glycoprotein 330 as an endocytic receptor for
RT apolipoprotein J/clusterin.";
RL J. Biol. Chem. 270:13070-13075(1995).
RN [29]
RP FUNCTION IN NEURITE OUTGROWTH, LRP-BINDING, AND CHARACTERIZATION OF VARIANT
RP AD2 ARG-130.
RX PubMed=8939961; DOI=10.1074/jbc.271.47.30121;
RA Fagan A.M., Bu G., Sun Y., Daugherty A., Holtzman D.M.;
RT "Apolipoprotein E-containing high density lipoprotein promotes neurite
RT outgrowth and is a ligand for the low density lipoprotein receptor-related
RT protein.";
RL J. Biol. Chem. 271:30121-30125(1996).
RN [30]
RP FUNCTION IN HDL CLEARANCE, AND HEPARAN SULFATE-BINDING.
RX PubMed=9395455; DOI=10.1074/jbc.272.50.31285;
RA Ji Z.S., Dichek H.L., Miranda R.D., Mahley R.W.;
RT "Heparan sulfate proteoglycans participate in hepatic lipase and
RT apolipoprotein E-mediated binding and uptake of plasma lipoproteins,
RT including high density lipoproteins.";
RL J. Biol. Chem. 272:31285-31292(1997).
RN [31]
RP FUNCTION, HEPARAN-SULFATE-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=9488694; DOI=10.1074/jbc.273.10.5645;
RA Burgess J.W., Gould D.R., Marcel Y.L.;
RT "The HepG2 extracellular matrix contains separate heparinase- and lipid-
RT releasable pools of ApoE. Implications for hepatic lipoprotein
RT metabolism.";
RL J. Biol. Chem. 273:5645-5654(1998).
RN [32]
RP TISSUE SPECIFICITY.
RX PubMed=10027417; DOI=10.1016/s0002-9440(10)65305-9;
RA Xu P.T., Gilbert J.R., Qiu H.L., Ervin J., Rothrock-Christian T.R.,
RA Hulette C., Schmechel D.E.;
RT "Specific regional transcription of apolipoprotein E in human brain
RT neurons.";
RL Am. J. Pathol. 154:601-611(1999).
RN [33]
RP GLYCATION AT LYS-93, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10452964; DOI=10.1016/s0925-4439(99)00047-2;
RA Shuvaev V.V., Fujii J., Kawasaki Y., Itoh H., Hamaoka R., Barbier A.,
RA Ziegler O., Siest G., Taniguchi N.;
RT "Glycation of apolipoprotein E impairs its binding to heparin:
RT identification of the major glycation site.";
RL Biochim. Biophys. Acta 1454:296-308(1999).
RN [34]
RP PTM, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX PubMed=11447277; DOI=10.1073/pnas.151254698;
RA Huang Y., Liu X.Q., Wyss-Coray T., Brecht W.J., Sanan D.A., Mahley R.W.;
RT "Apolipoprotein E fragments present in Alzheimer's disease brains induce
RT neurofibrillary tangle-like intracellular inclusions in neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8838-8843(2001).
RN [35]
RP FUNCTION, LRP8-BINDING, AND CHARACTERIZATION OF VARIANT CYS-176.
RX PubMed=12950167; DOI=10.1021/bi027093c;
RA Li X., Kypreos K., Zanni E.E., Zannis V.;
RT "Domains of apoE required for binding to apoE receptor 2 and to
RT phospholipids: implications for the functions of apoE in the brain.";
RL Biochemistry 42:10406-10417(2003).
RN [36]
RP FUNCTION IN REVERSE CHOLESTEROL TRANSPORT, AND INTERACTION WITH ABCA1.
RX PubMed=14754908; DOI=10.1194/jlr.m300418-jlr200;
RA Krimbou L., Denis M., Haidar B., Carrier M., Marcil M., Genest J. Jr.;
RT "Molecular interactions between apoE and ABCA1: impact on apoE
RT lipidation.";
RL J. Lipid Res. 45:839-848(2004).
RN [37]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-212; THR-307 AND SER-308, AND
RP STRUCTURE OF CARBOHYDRATES.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [38]
RP FUNCTION, LRP1-BINDING, AND REGION.
RX PubMed=20030366; DOI=10.1021/bi9017208;
RA Guttman M., Prieto J.H., Croy J.E., Komives E.A.;
RT "Decoding of lipoprotein-receptor interactions: properties of ligand
RT binding modules governing interactions with apolipoprotein E.";
RL Biochemistry 49:1207-1216(2010).
RN [39]
RP GLYCOSYLATION AT SER-308.
RX PubMed=20511397; DOI=10.1074/mcp.m900430-mcp200;
RA Lee Y., Kockx M., Raftery M.J., Jessup W., Griffith R., Kritharides L.;
RT "Glycosylation and sialylation of macrophage-derived human apolipoprotein E
RT analyzed by SDS-PAGE and mass spectrometry: evidence for a novel site of
RT glycosylation on Ser290.";
RL Mol. Cell. Proteomics 9:1968-1981(2010).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [41]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [42]
RP FUNCTION IN LIPOPROTEIN CLEARANCE, AND HEPARAN-SULFATE PROTEOGLYCANS
RP BINDING.
RX PubMed=23676495; DOI=10.1172/jci67398;
RA Gonzales J.C., Gordts P.L., Foley E.M., Esko J.D.;
RT "Apolipoproteins E and AV mediate lipoprotein clearance by hepatic
RT proteoglycans.";
RL J. Clin. Invest. 123:2742-2751(2013).
RN [43]
RP GLYCOSYLATION AT THR-26; THR-36 AND SER-314, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
RN [44]
RP FUNCTION IN CHOLESTEROL EFFLUX, AND INTERACTION WITH APP/A4 AMYLOID-BETA
RP PEPTIDE.
RX PubMed=23620513; DOI=10.1073/pnas.1220484110;
RA Verghese P.B., Castellano J.M., Garai K., Wang Y., Jiang H., Shah A.,
RA Bu G., Frieden C., Holtzman D.M.;
RT "ApoE influences amyloid-beta (Abeta) clearance despite minimal apoE/Abeta
RT association in physiological conditions.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1807-E1816(2013).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-147, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [46]
RP INTERACTION WITH HCV ENVELOPE GLYCOPROTEIN E2 (MICROBIAL INFECTION), AND
RP FUNCTION MICROBIAL INFECTION).
RX PubMed=25122793; DOI=10.1128/jvi.01660-14;
RA Lee J.Y., Acosta E.G., Stoeck I.K., Long G., Hiet M.S., Mueller B.,
RA Fackler O.T., Kallis S., Bartenschlager R.;
RT "Apolipoprotein E likely contributes to a maturation step of infectious
RT hepatitis C virus particles and interacts with viral envelope
RT glycoproteins.";
RL J. Virol. 88:12422-12437(2014).
RN [47]
RP PHOSPHORYLATION AT SER-147.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [48]
RP FUNCTION IN APP TRANSCRIPTION, AND CHARACTERIZATION OF VARIANT AD2 ARG-130.
RX PubMed=28111074; DOI=10.1016/j.cell.2016.12.044;
RA Huang Y.A., Zhou B., Wernig M., Suedhof T.C.;
RT "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and
RT Abeta Secretion.";
RL Cell 168:427-441(2017).
RN [49]
RP INTERACTION WITH HCV ENVELOPE GLYCOPROTEIN E2 (MICROBIAL INFECTION), AND
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=29695434; DOI=10.1128/jvi.00211-18;
RA Kim J.Y., Ou J.J.;
RT "Regulation of Apolipoprotein E Trafficking by Hepatitis C Virus-Induced
RT Autophagy.";
RL J. Virol. 92:e00211-e00218(2018).
RN [50]
RP FUNCTION, SUBCELLULAR LOCATION, AND ROLE IN TUMOR CELL INFILTRATION.
RX PubMed=30333625; DOI=10.1038/s41586-018-0615-z;
RA Deng M., Gui X., Kim J., Xie L., Chen W., Li Z., He L., Chen Y., Chen H.,
RA Luo W., Lu Z., Xie J., Churchill H., Xu Y., Zhou Z., Wu G., Yu C., John S.,
RA Hirayasu K., Nguyen N., Liu X., Huang F., Li L., Deng H., Tang H.,
RA Sadek A.H., Zhang L., Huang T., Zou Y., Chen B., Zhu H., Arase H., Xia N.,
RA Jiang Y., Collins R., You M.J., Homsi J., Unni N., Lewis C., Chen G.Q.,
RA Fu Y.X., Liao X.C., An Z., Zheng J., Zhang N., Zhang C.C.;
RT "LILRB4 signalling in leukaemia cells mediates T cell suppression and
RT tumour infiltration.";
RL Nature 562:605-609(2018).
RN [51] {ECO:0007744|PDB:1LPE}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 41-184, FUNCTION, AND REGION.
RX PubMed=2063194; DOI=10.1126/science.2063194;
RA Wilson C., Wardell M.R., Weisgraber K.H., Mahley R.W., Agard D.A.;
RT "Three-dimensional structure of the LDL receptor-binding domain of human
RT apolipoprotein E.";
RL Science 252:1817-1822(1991).
RN [52] {ECO:0007744|PDB:1LE4}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 41-184 OF VARIANT AD2 ARG-130,
RP CHARACTERIZATION OF VARIANT AD2 ARG-130, MUTAGENESIS OF ARG-79 AND GLU-127,
RP AND REGION.
RX PubMed=8071364; DOI=10.1016/s0021-9258(17)31797-0;
RA Dong L.M., Wilson C., Wardell M.R., Simmons T., Mahley R.W.,
RA Weisgraber K.H., Agard D.A.;
RT "Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein
RT preferences of the E3 and E4 isoforms.";
RL J. Biol. Chem. 269:22358-22365(1994).
RN [53] {ECO:0007744|PDB:1LE2}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 41-184 OF VARIANT CYS-176, AND
RP CHARACTERIZATION OF VARIANT CYS-176.
RX PubMed=7994571; DOI=10.1016/s0969-2126(00)00072-1;
RA Wilson C., Mau T., Weisgraber K.H., Wardell M.R., Mahley R.W., Agard D.A.;
RT "Salt bridge relay triggers defective LDL receptor binding by a mutant
RT apolipoprotein.";
RL Structure 2:713-718(1994).
RN [54] {ECO:0007744|PDB:1NFN, ECO:0007744|PDB:1NFO}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 19-209 OF VARIANT CYS-176,
RP MUTAGENESIS OF ASP-172, CHARACTERIZATION OF VARIANT CYS-176, FUNCTION, AND
RP LDLR-BINDING.
RX PubMed=8756331; DOI=10.1038/nsb0896-718;
RA Dong L.-M., Parkin S., Trakhanov S.D., Rupp B., Simmons T., Arnold K.S.,
RA Newhouse Y.M., Innerarity T.L., Weisgraber K.H.;
RT "Novel mechanism for defective receptor binding of apolipoprotein E2 in
RT type III hyperlipoproteinemia.";
RL Nat. Struct. Biol. 3:718-722(1996).
RN [55] {ECO:0007744|PDB:1BZ4, ECO:0007744|PDB:1OR2, ECO:0007744|PDB:1OR3}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 19-183.
RX PubMed=10850798; DOI=10.1110/ps.9.5.886;
RA Segelke B.W., Forstner M., Knapp M., Trakhanov S.D., Parkin S.,
RA Newhouse Y.M., Bellamy H.D., Weisgraber K.H., Rupp B.;
RT "Conformational flexibility in the apolipoprotein E amino-terminal domain
RT structure determined from three new crystal forms: implications for lipid
RT binding.";
RL Protein Sci. 9:886-897(2000).
RN [56] {ECO:0007744|PDB:1B68}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 19-209 OF VARIANT AD2 ARG-130.
RX PubMed=11258893; DOI=10.1021/bi002417n;
RA Dong J., Peters-Libeu C.A., Weisgraber K.H., Segelke B.W., Rupp B.,
RA Capila I., Hernaiz M.J., LeBrun L.A., Linhardt R.J.;
RT "Interaction of the N-terminal domain of apolipoprotein E4 with heparin.";
RL Biochemistry 40:2826-2834(2001).
RN [57] {ECO:0007744|PDB:2KNY}
RP STRUCTURE BY NMR OF 147-167 IN COMPLEX WITH LRP1, FUNCTION, AND
RP LRP1-BINDING.
RX PubMed=20303980; DOI=10.1016/j.jmb.2010.03.022;
RA Guttman M., Prieto J.H., Handel T.M., Domaille P.J., Komives E.A.;
RT "Structure of the minimal interface between ApoE and LRP.";
RL J. Mol. Biol. 398:306-319(2010).
RN [58]
RP VARIANT HLPP3 262-GLU-GLU-263 DELINS LYS-LYS.
RX PubMed=2738044; DOI=10.1093/oxfordjournals.jbchem.a122618;
RA Maeda H., Nakamura H., Kobori S., Okada M., Mori H., Niki H., Ogura T.,
RA Hiraga S.;
RT "Identification of human apolipoprotein E variant gene: apolipoprotein E7
RT (Glu244,245----Lys244,245).";
RL J. Biochem. 105:51-54(1989).
RN [59]
RP VARIANT LYS-21.
RX PubMed=2760009; DOI=10.1093/oxfordjournals.jbchem.a122692;
RA Maeda H., Nakamura H., Kobori S., Okada M., Niki H., Ogura T., Hiraga S.;
RT "Molecular cloning of a human apolipoprotein E variant: E5 (Glu-3-->Lys).";
RL J. Biochem. 105:491-493(1989).
RN [60]
RP VARIANTS HLPP3 ARG-130 AND GLU-VAL-GLN-ALA-MET-LEU-GLY-145 INS.
RX PubMed=2556398; DOI=10.1016/s0021-9258(19)30067-5;
RA Wardell M.R., Weisgraber K.H., Havekes L.M., Rall S.C. Jr.;
RT "Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a
RT tandem repeat of residues 121-127.";
RL J. Biol. Chem. 264:21205-21210(1989).
RN [61]
RP VARIANT HLPP3 HIS-163.
RX PubMed=2101409; DOI=10.2169/internalmedicine1962.29.587;
RA Suehiro T., Yoshida K., Yamano T., Ohno F.;
RT "Identification and characterization of a new variant of apolipoprotein E
RT (apo E-Kochi).";
RL Jpn. J. Med. 29:587-594(1990).
RN [62]
RP VARIANT CYS-246.
RX PubMed=2341812;
RA Wardell M.R., Rall S.C. Jr., Brennan S.O., Nye E.R., George P.M.,
RA Janus E.D., Weisgraber K.H.;
RT "Apolipoprotein E2-Dunedin (228 Arg replaced by Cys): an apolipoprotein E2
RT variant with normal receptor-binding activity.";
RL J. Lipid Res. 31:535-543(1990).
RN [63]
RP VARIANTS HLPP3 LYS-31 AND CYS-163.
RX PubMed=1674745; DOI=10.1016/s0021-9258(18)99249-5;
RA Lohse P., Mann W.A., Stein E.A., Brewer H.B. Jr.;
RT "Apolipoprotein E-4 Philadelphia (Glu-13-->Lys,Arg-145-->Cys). Homozygosity
RT for two rare point mutations in the apolipoprotein E gene combined with
RT severe type III hyperlipoproteinemia.";
RL J. Biol. Chem. 266:10479-10484(1991).
RN [64]
RP VARIANT APOE5 FRENCH-CANADIAN LYS-31.
RX PubMed=1713245;
RA Mailly F., Xu C.F., Xhignesse M., Lussier-Cacan S., Talmud P.J.,
RA Davignon J., Humphries S.E., Nestruck A.C.;
RT "Characterization of a new apolipoprotein E5 variant detected in two
RT French-Canadian subjects.";
RL J. Lipid Res. 32:613-620(1991).
RN [65]
RP CHARACTERIZATION OF VARIANT LYS-21, FUNCTION, AND LDLR-BINDING.
RX PubMed=1530612; DOI=10.1016/0006-291x(92)91321-g;
RA Dong L.M., Yamamura T., Tajima S., Yamamoto A.;
RT "Site-directed mutagenesis of an apolipoprotein E mutant, apo E5(Glu3----
RT Lys) and its binding to low density lipoprotein receptors.";
RL Biochem. Biophys. Res. Commun. 187:1180-1186(1992).
RN [66]
RP VARIANT HLPP3 228-TRP--HIS-317 DEL.
RX PubMed=1361196;
RA Lohse P., Brewer H.B. III, Meng M.S., Skarlatos S.I., LaRosa J.C.,
RA Brewer H.B. Jr.;
RT "Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due
RT to a premature stop codon in the apolipoprotein E gene.";
RL J. Lipid Res. 33:1583-1590(1992).
RN [67]
RP VARIANTS GLU-254; GLY-269; GLU-270; HIS-292 AND ARG-314.
RX PubMed=8488843;
RA van den Maagdenberg A.M.J.M., Weng W., de Bruijn I.H., de Knijff P.,
RA Funke H., Smelt A.H.M., Leuven J.A.G., van 't Hooft F.M., Assmann G.,
RA Hofker M.H., Havekes L.M., Frants R.R.;
RT "Characterization of five new mutants in the carboxyl-terminal domain of
RT human apolipoprotein E: no cosegregation with severe hyperlipidemia.";
RL Am. J. Hum. Genet. 52:937-946(1993).
RN [68]
RP VARIANTS LYS-99 AND ARG-130.
RX PubMed=8125051; DOI=10.1002/elps.11501401164;
RA Ruzicka V., Maerz W., Russ A., Fisher E., Mondorf W., Gross W.;
RT "Characterization of the gene for apolipoprotein E5-Frankfurt (Gln81->Lys,
RT Cys112->Arg) by polymerase chain reaction, restriction isotyping, and
RT temperature gradient gel electrophoresis.";
RL Electrophoresis 14:1032-1037(1993).
RN [69]
RP CHARACTERIZATION OF VARIANT GLU-VAL-GLN-ALA-MET-LEU-GLY-145 INS.
RX PubMed=8468528;
RA Fazio S., Horie Y., Weisgraber K.H., Havekes L.M., Rall S.C. Jr.;
RT "Preferential association of apolipoprotein E Leiden with very low density
RT lipoproteins of human plasma.";
RL J. Lipid Res. 34:447-453(1993).
RN [70]
RP INVOLVEMENT IN AD2, AND VARIANT AD2 ARG-130.
RX PubMed=8346443; DOI=10.1126/science.8346443;
RA Corder E.H., Saunders A.M., Strittmatter W.J., Schmechel D.E.,
RA Gaskell P.C., Small G.W., Roses A.D., Haines J.L., Pericak-Vance M.A.;
RT "Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's
RT disease in late onset families.";
RL Science 261:921-923(1993).
RN [71]
RP VARIANTS HLPP3 ARG-130; SER-154; CYS-160 AND CYS-176, AND VARIANT ASP-145.
RX PubMed=8287539;
RA Richard P., Thomas G., de Zulueta M.P., de Gennes J.-L., Thomas M.,
RA Cassaigne A., Bereziat G., Iron A.;
RT "Common and rare genotypes of human apolipoprotein E determined by specific
RT restriction profiles of polymerase chain reaction-amplified DNA.";
RL Clin. Chem. 40:24-29(1994).
RN [72]
RP VARIANT HLPP3 GLU-164, CHARACTERIZATION OF VARIANT HLPP3 GLU-164 AND
RP CYS-176, FUNCTION, LDLR-BINDING, AND HEPARIN-BINDING.
RX PubMed=7635945; DOI=10.1172/jci118096;
RA Mann W.A., Lohse P., Gregg R.E., Ronan R., Hoeg J.M., Zech L.A.,
RA Brewer H.B. Jr.;
RT "Dominant expression of type III hyperlipoproteinemia. Pathophysiological
RT insights derived from the structural and kinetic characteristics of ApoE-1
RT (Lys146-->Glu).";
RL J. Clin. Invest. 96:1100-1107(1995).
RN [73]
RP VARIANT GLN-242.
RX PubMed=8664327; DOI=10.1016/0005-2760(96)00014-8;
RA Moriyama K., Sasaki J., Takada Y., Arakawa F., Matsunaga A., Ito Y.,
RA Arakawa K.;
RT "Characterization of a novel variant of apolipoprotein E, E2 Fukuoka (Arg-
RT 224 --> Gln) in a hyperlipidemic patient with xanthomatosis.";
RL Biochim. Biophys. Acta 1301:185-190(1996).
RN [74]
RP VARIANT LPG PRO-163.
RX PubMed=9176854; DOI=10.1681/asn.v85820;
RA Oikawa S., Matsunaga A., Saito T., Sato H., Seki T., Hoshi K., Hayasaka K.,
RA Kotake H., Midorikawa H., Sekikawa A., Hara S., Abe K., Toyota T.,
RA Jingami H., Nakamura H., Sasaki J.;
RT "Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated
RT with lipoprotein glomerulopathy.";
RL J. Am. Soc. Nephrol. 8:820-823(1997).
RN [75]
RP VARIANTS ARG-130 AND GLY-269.
RX PubMed=9360638; DOI=10.1016/s1383-5726(97)00009-5;
RA Kang A.K., Jenkins D.J.A., Wolever T.M.S., Huff M.W., Maguire G.F.,
RA Connelly P.W., Hegele R.A.;
RT "Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients
RT with hyperlipidemia and coronary heart disease.";
RL Mutat. Res. 382:57-65(1997).
RN [76]
RP VARIANT LPG CYS-43.
RX PubMed=10432380; DOI=10.1046/j.1523-1755.1999.00572.x;
RA Matsunaga A., Sasaki J., Komatsu T., Kanatsu K., Tsuji E., Moriyama K.,
RA Koga T., Arakawa K., Oikawa S., Saito T., Kita T., Doi T.;
RT "A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein
RT glomerulopathy.";
RL Kidney Int. 56:421-427(1999).
RN [77]
RP CHARACTERIZATION OF VARIANT LPG PRO-163, AND CHARACTERIZATION OF VARIANT
RP AD2 ARG-130.
RX PubMed=10903326; DOI=10.1074/jbc.m005906200;
RA Ishigaki Y., Oikawa S., Suzuki T., Usui S., Magoori K., Kim D.H.,
RA Suzuki H., Sasaki J., Sasano H., Okazaki M., Toyota T., Saito T.,
RA Yamamoto T.T.;
RT "Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops
RT lipoprotein glomerulopathy in ApoE-deficient mice.";
RL J. Biol. Chem. 275:31269-31273(2000).
RN [78]
RP VARIANT SBHD LEU-167 DEL.
RX PubMed=11095479; DOI=10.1210/jcem.85.11.6981;
RA Nguyen T.T., Kruckeberg K.E., O'Brien J.F., Ji Z.-S., Karnes P.S.,
RA Crotty T.B., Hay I.D., Mahley R.W., O'Brien T.;
RT "Familial splenomegaly: macrophage hypercatabolism of lipoproteins
RT associated with apolipoprotein E mutation [apolipoprotein E (delta149
RT Leu)].";
RL J. Clin. Endocrinol. Metab. 85:4354-4358(2000).
RN [79]
RP VARIANT VAL-124.
RX PubMed=12864777; DOI=10.1046/j.1365-2362.2003.01180.x;
RA Miserez A.R., Scharnagl H., Muller P.Y., Mirsaidi R., Stahelin H.B.,
RA Monsch A., Marz W., Hoffmann M.M.;
RT "Apolipoprotein E3Basel: new insights into a highly conserved protein
RT region.";
RL Eur. J. Clin. Invest. 33:677-685(2003).
RN [80]
RP VARIANTS ARG-130 AND CYS-176.
RX PubMed=12966036; DOI=10.1093/hmg/ddg314;
RA Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S.,
RA Alvin G.B., Das K., Gilliam T.C.;
RT "Association of extreme blood lipid profile phenotypic variation with 11
RT reverse cholesterol transport genes and 10 non-genetic cardiovascular
RT disease risk factors.";
RL Hum. Mol. Genet. 12:2733-2743(2003).
RN [81]
RP VARIANT SBHD LEU-167 DEL.
RX PubMed=16094309; DOI=10.1038/sj.ejhg.5201480;
RA Faivre L., Saugier-Veber P., Pais de Barros J.-P., Verges B., Couret B.,
RA Lorcerie B., Thauvin C., Charbonnier F., Huet F., Gambert P., Frebourg T.,
RA Duvillard L.;
RT "Variable expressivity of the clinical and biochemical phenotype associated
RT with the apolipoprotein E p.Leu149del mutation.";
RL Eur. J. Hum. Genet. 13:1186-1191(2005).
RN [82]
RP VARIANT LPG CYS-43.
RX PubMed=18077821; DOI=10.1056/nejmc072088;
RA Rovin B.H., Roncone D., McKinley A., Nadasdy T., Korbet S.M.,
RA Schwartz M.M.;
RT "APOE Kyoto mutation in European Americans with lipoprotein
RT glomerulopathy.";
RL N. Engl. J. Med. 357:2522-2524(2007).
RN [83]
RP VARIANT HIS-64, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22028381; DOI=10.1093/jmcb/mjr024;
RA Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X.,
RA Zeng R., Wu J.R.;
RT "Quantitative detection of single amino acid polymorphisms by targeted
RT proteomics.";
RL J. Mol. Cell Biol. 3:309-315(2011).
RN [84]
RP VARIANT HLPP3 SER-154, AND VARIANT SBHD LEU-167 DEL.
RX PubMed=22481068; DOI=10.1016/j.atherosclerosis.2012.03.011;
RA Solanas-Barca M., de Castro-Oros I., Mateo-Gallego R., Cofan M., Plana N.,
RA Puzo J., Burillo E., Martin-Fuentes P., Ros E., Masana L., Pocovi M.,
RA Civeira F., Cenarro A.;
RT "Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and
RT a clinical diagnosis of familial combined hyperlipidemia.";
RL Atherosclerosis 222:449-455(2012).
RN [85]
RP VARIANT SBHD LEU-167 DEL.
RX PubMed=24267230; DOI=10.1016/j.atherosclerosis.2013.09.007;
RA Awan Z., Choi H.Y., Stitziel N., Ruel I., Bamimore M.A., Husa R.,
RA Gagnon M.H., Wang R.H., Peloso G.M., Hegele R.A., Seidah N.G.,
RA Kathiresan S., Genest J.;
RT "APOE p.Leu167del mutation in familial hypercholesterolemia.";
RL Atherosclerosis 231:218-222(2013).
RN [86]
RP VARIANT SBHD LEU-167 DEL.
RX PubMed=22949395; DOI=10.1002/humu.22215;
RA Marduel M., Ouguerram K., Serre V., Bonnefont-Rousselot D.,
RA Marques-Pinheiro A., Erik Berge K., Devillers M., Luc G., Lecerf J.M.,
RA Tosolini L., Erlich D., Peloso G.M., Stitziel N., Nitchke P., Jais J.P.,
RA Abifadel M., Kathiresan S., Leren T.P., Rabes J.P., Boileau C., Varret M.;
RT "Description of a large family with autosomal dominant hypercholesterolemia
RT associated with the APOE p.Leu167del mutation.";
RL Hum. Mutat. 34:83-87(2013).
RN [87]
RP VARIANTS PRO-46 AND ASP-145, VARIANT HLPP3 CYS-163, AND VARIANT SBHD
RP LEU-167 DEL.
RX PubMed=26802169; DOI=10.1194/jlr.p055699;
RA Wintjens R., Bozon D., Belabbas K., Mbou F., Girardet J.P., Tounian P.,
RA Jolly M., Boccara F., Cohen A., Karsenty A., Dubern B., Carel J.C.,
RA Azar-Kolakez A., Feillet F., Labarthe F., Gorsky A.M., Horovitz A.,
RA Tamarindi C., Kieffer P., Lienhardt A., Lascols O., Di Filippo M.,
RA Dufernez F.;
RT "Global molecular analysis and APOE mutations in a cohort of autosomal
RT dominant hypercholesterolemia patients in France.";
RL J. Lipid Res. 57:482-491(2016).
RN [88]
RP REVIEW, AND VARIANTS LYS-31; ARG-102; ARG-130; GLN-152 AND CYS-154.
RX PubMed=7833947; DOI=10.1002/humu.1380040303;
RA de Knijff P., van den Maagdenberg A.M.J.M., Frants R.R., Havekes L.M.;
RT "Genetic heterogeneity of apolipoprotein E and its influence on plasma
RT lipid and lipoprotein levels.";
RL Hum. Mutat. 4:178-194(1994).
RN [89]
RP REVIEW, POLYMORPHISM, AND TISSUE SPECIFICITY.
RX PubMed=25173806; DOI=10.1016/j.nbd.2014.08.025;
RA Huang Y., Mahley R.W.;
RT "Apolipoprotein E: structure and function in lipid metabolism,
RT neurobiology, and Alzheimer's diseases.";
RL Neurobiol. Dis. 72:3-12(2014).
RN [90]
RP REVIEW, FUNCTION, AND PTM.
RX PubMed=29516132; DOI=10.1007/s00109-018-1632-y;
RA Kockx M., Traini M., Kritharides L.;
RT "Cell-specific production, secretion, and function of apolipoprotein E.";
RL J. Mol. Med. 96:361-371(2018).
RN [91]
RP POLYMORPHISM, AND VARIANT ARG-130.
RX PubMed=33450186; DOI=10.1016/j.stem.2020.12.018;
RA Wang C., Zhang M., Garcia G. Jr., Tian E., Cui Q., Chen X., Sun G.,
RA Wang J., Arumugaswami V., Shi Y.;
RT "ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response.";
RL Cell Stem Cell 0:0-0(2021).
CC -!- FUNCTION: APOE is an apolipoprotein, a protein associating with lipid
CC particles, that mainly functions in lipoprotein-mediated lipid
CC transport between organs via the plasma and interstitial fluids
CC (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core
CC component of plasma lipoproteins and is involved in their production,
CC conversion and clearance (PubMed:6860692, PubMed:2762297,
CC PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908,
CC PubMed:23620513). Apoliproteins are amphipathic molecules that interact
CC both with lipids of the lipoprotein particle core and the aqueous
CC environment of the plasma (PubMed:6860692, PubMed:2762297,
CC PubMed:9395455). As such, APOE associates with chylomicrons,
CC chylomicron remnants, very low density lipoproteins (VLDL) and
CC intermediate density lipoproteins (IDL) but shows a preferential
CC binding to high-density lipoproteins (HDL) (PubMed:6860692,
CC PubMed:1911868). It also binds a wide range of cellular receptors
CC including the LDL receptor/LDLR, the LDL receptor-related proteins
CC LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR
CC that mediate the cellular uptake of the APOE-containing lipoprotein
CC particles (PubMed:2762297, PubMed:1917954, PubMed:7768901,
CC PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194,
CC PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945).
CC Finally, APOE has also a heparin-binding activity and binds heparan-
CC sulfate proteoglycans on the surface of cells, a property that supports
CC the capture and the receptor-mediated uptake of APOE-containing
CC lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495,
CC PubMed:7635945). A main function of APOE is to mediate lipoprotein
CC clearance through the uptake of chylomicrons, VLDLs, and HDLs by
CC hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455,
CC PubMed:23676495, PubMed:29516132). APOE is also involved in the
CC biosynthesis by the liver of VLDLs as well as their uptake by
CC peripheral tissues ensuring the delivery of triglycerides and energy
CC storage in muscle, heart and adipose tissues (PubMed:2762297,
CC PubMed:29516132). By participating in the lipoprotein-mediated
CC distribution of lipids among tissues, APOE plays a critical role in
CC plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954,
CC PubMed:29516132). APOE is also involved in two steps of reverse
CC cholesterol transport, the HDLs-mediated transport of cholesterol from
CC peripheral tissues to the liver, and thereby plays an important role in
CC cholesterol homeostasis (PubMed:9395455, PubMed:14754908,
CC PubMed:23620513). First, it is functionally associated with ABCA1 in
CC the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513).
CC Second, it is enriched in circulating HDLs and mediates their uptake by
CC hepatocytes (PubMed:9395455). APOE also plays an important role in
CC lipid transport in the central nervous system, regulating neuron
CC survival and sprouting (PubMed:8939961, PubMed:25173806). APOE is also
CC involved in innate and adaptive immune responses, controlling for
CC instance the survival of myeloid-derived suppressor cells (By
CC similarity). Binds to the immune cell receptor LILRB4
CC (PubMed:30333625). APOE may also play a role in transcription
CC regulation through a receptor-dependent and cholesterol-independent
CC mechanism, that activates MAP3K12 and a non-canonical MAPK signal
CC transduction pathway that results in enhanced AP-1-mediated
CC transcription of APP (PubMed:28111074). {ECO:0000250|UniProtKB:P08226,
CC ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:14754908,
CC ECO:0000269|PubMed:1530612, ECO:0000269|PubMed:1911868,
CC ECO:0000269|PubMed:1917954, ECO:0000269|PubMed:20030366,
CC ECO:0000269|PubMed:20303980, ECO:0000269|PubMed:2063194,
CC ECO:0000269|PubMed:23620513, ECO:0000269|PubMed:23676495,
CC ECO:0000269|PubMed:2762297, ECO:0000269|PubMed:28111074,
CC ECO:0000269|PubMed:30333625, ECO:0000269|PubMed:6860692,
CC ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7768901,
CC ECO:0000269|PubMed:8756331, ECO:0000269|PubMed:8939961,
CC ECO:0000269|PubMed:9395455, ECO:0000269|PubMed:9488694,
CC ECO:0000303|PubMed:25173806, ECO:0000303|PubMed:29516132}.
CC -!- FUNCTION: (Microbial infection) Through its interaction with HCV
CC envelope glycoprotein E2, participates in the attachment of HCV to
CC HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface
CC and to the assembly, maturation and infectivity of HCV viral particles
CC (PubMed:25122793, PubMed:29695434). This interaction is probably
CC promoted via the up-regulation of cellular autophagy by the virus
CC (PubMed:29695434). {ECO:0000269|PubMed:25122793,
CC ECO:0000269|PubMed:29695434}.
CC -!- SUBUNIT: Homotetramer (PubMed:8340399). May interact with ABCA1;
CC functionally associated with ABCA1 in the biogenesis of HDLs
CC (PubMed:14754908). May interact with APP/A4 amyloid-beta peptide; the
CC interaction is extremely stable in vitro but its physiological
CC significance is unclear (PubMed:8367470, PubMed:23620513). May interact
CC with MAPT (PubMed:7972031). May interact with MAP2 (PubMed:7891887). In
CC the cerebrospinal fluid, interacts with secreted SORL1
CC (PubMed:30448281). {ECO:0000269|PubMed:14754908,
CC ECO:0000269|PubMed:23620513, ECO:0000269|PubMed:30448281,
CC ECO:0000269|PubMed:7891887, ECO:0000269|PubMed:7972031,
CC ECO:0000269|PubMed:8340399, ECO:0000269|PubMed:8367470}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus (HCV)
CC envelope glycoprotein E2; this interaction is required for HCV
CC infectivity and production. {ECO:0000269|PubMed:25122793,
CC ECO:0000269|PubMed:29695434}.
CC -!- INTERACTION:
CC P02649; Q9UIJ7: AK3; NbExp=3; IntAct=EBI-1222467, EBI-3916527;
CC P02649; Q06481-5: APLP2; NbExp=3; IntAct=EBI-1222467, EBI-25646567;
CC P02649; PRO_0000000093 [P05067]: APP; NbExp=4; IntAct=EBI-1222467, EBI-2431589;
CC P02649; Q9HBG4: ATP6V0A4; NbExp=3; IntAct=EBI-1222467, EBI-25832286;
CC P02649; Q9H6J7-2: C11orf49; NbExp=3; IntAct=EBI-1222467, EBI-13328871;
CC P02649; Q9NUB4: C20orf141; NbExp=3; IntAct=EBI-1222467, EBI-9088162;
CC P02649; Q16543: CDC37; NbExp=3; IntAct=EBI-1222467, EBI-295634;
CC P02649; P08603: CFH; NbExp=8; IntAct=EBI-1222467, EBI-1223708;
CC P02649; Q9UBD9: CLCF1; NbExp=3; IntAct=EBI-1222467, EBI-2880701;
CC P02649; Q8IUW6: CLSTN3; NbExp=3; IntAct=EBI-1222467, EBI-25832219;
CC P02649; P26441: CNTF; NbExp=3; IntAct=EBI-1222467, EBI-1050897;
CC P02649; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-1222467, EBI-3508943;
CC P02649; Q9BQ95: ECSIT; NbExp=4; IntAct=EBI-1222467, EBI-712452;
CC P02649; Q9Y6C2-2: EMILIN1; NbExp=3; IntAct=EBI-1222467, EBI-11748557;
CC P02649; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-1222467, EBI-6425864;
CC P02649; Q8IY40: GRIK2; NbExp=3; IntAct=EBI-1222467, EBI-25832107;
CC P02649; O75409: H2AP; NbExp=3; IntAct=EBI-1222467, EBI-6447217;
CC P02649; P00738: HP; NbExp=7; IntAct=EBI-1222467, EBI-1220767;
CC P02649; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-1222467, EBI-1108377;
CC P02649; P01130: LDLR; NbExp=4; IntAct=EBI-1222467, EBI-988319;
CC P02649; P09382: LGALS1; NbExp=3; IntAct=EBI-1222467, EBI-1048875;
CC P02649; Q07954: LRP1; NbExp=23; IntAct=EBI-1222467, EBI-1046087;
CC P02649; Q14114: LRP8; NbExp=2; IntAct=EBI-1222467, EBI-2681187;
CC P02649; Q14114-3: LRP8; NbExp=3; IntAct=EBI-1222467, EBI-25832196;
CC P02649; P11137-4: MAP2; NbExp=3; IntAct=EBI-1222467, EBI-25832133;
CC P02649; P10636-6: MAPT; NbExp=3; IntAct=EBI-1222467, EBI-7796455;
CC P02649; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-1222467, EBI-9092052;
CC P02649; P02795: MT2A; NbExp=3; IntAct=EBI-1222467, EBI-996616;
CC P02649; Q53EL6: PDCD4; NbExp=3; IntAct=EBI-1222467, EBI-935824;
CC P02649; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-1222467, EBI-438710;
CC P02649; P52756: RBM5; NbExp=3; IntAct=EBI-1222467, EBI-714003;
CC P02649; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-1222467, EBI-21535400;
CC P02649; Q8WTV0-2: SCARB1; NbExp=3; IntAct=EBI-1222467, EBI-21529758;
CC P02649; P37840: SNCA; NbExp=11; IntAct=EBI-1222467, EBI-985879;
CC P02649; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-1222467, EBI-2510414;
CC P02649; P50502: ST13; NbExp=3; IntAct=EBI-1222467, EBI-357285;
CC P02649; O75069: TMCC2; NbExp=5; IntAct=EBI-1222467, EBI-726731;
CC P02649; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-1222467, EBI-2505861;
CC P02649; Q9NZC2: TREM2; NbExp=4; IntAct=EBI-1222467, EBI-14036387;
CC P02649; Q6PID6: TTC33; NbExp=3; IntAct=EBI-1222467, EBI-2555404;
CC P02649; Q8TBC4: UBA3; NbExp=3; IntAct=EBI-1222467, EBI-717567;
CC P02649; Q9NYH9: UTP6; NbExp=3; IntAct=EBI-1222467, EBI-749211;
CC P02649; P17028: ZNF24; NbExp=3; IntAct=EBI-1222467, EBI-707773;
CC P02649; PRO_0000037570 [P27958]; Xeno; NbExp=4; IntAct=EBI-1222467, EBI-6904269;
CC PRO_0000001987; P10636: MAPT; NbExp=3; IntAct=EBI-9209835, EBI-366182;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2498325,
CC ECO:0000269|PubMed:30333625}. Secreted, extracellular space
CC {ECO:0000269|PubMed:8340399}. Secreted, extracellular space,
CC extracellular matrix {ECO:0000269|PubMed:9488694}. Note=In the plasma,
CC APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL
CC and HDL lipoproteins (PubMed:1911868, PubMed:8340399). Lipid poor
CC oligomeric APOE is associated with the extracellular matrix in a
CC calcium- and heparan-sulfate proteoglycans-dependent manner
CC (PubMed:9488694). Lipidation induces the release from the extracellular
CC matrix (PubMed:9488694). {ECO:0000269|PubMed:1911868,
CC ECO:0000269|PubMed:8340399, ECO:0000269|PubMed:9488694}.
CC -!- TISSUE SPECIFICITY: Produced by several tissues and cell types and
CC mainly found associated with lipid particles in the plasma, the
CC interstitial fluid and lymph (PubMed:25173806). Mainly synthesized by
CC liver hepatocytes (PubMed:25173806). Significant quantities are also
CC produced in brain, mainly by astrocytes and glial cells in the cerebral
CC cortex, but also by neurons in frontal cortex and hippocampus
CC (PubMed:3115992, PubMed:10027417). It is also expressed by cells of the
CC peripheral nervous system (PubMed:10027417, PubMed:25173806). Also
CC expressed by adrenal gland, testis, ovary, skin, kidney, spleen and
CC adipose tissue and macrophages in various tissues (PubMed:25173806).
CC {ECO:0000269|PubMed:10027417, ECO:0000269|PubMed:3115992,
CC ECO:0000303|PubMed:25173806}.
CC -!- PTM: APOE exists as multiple glycosylated and sialylated glycoforms
CC within cells and in plasma (PubMed:29516132). The extent of
CC glycosylation and sialylation are tissue and context specific
CC (PubMed:29516132). Plasma APOE undergoes desialylation and is less
CC glycosylated and sialylated than the cellular form (PubMed:2498325,
CC PubMed:19838169, PubMed:20511397, PubMed:23234360). Glycosylation is
CC not required for proper expression and secretion (PubMed:2498325). O-
CC glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-
CC 314 are minor glycosylation sites compared to Ser-308 (PubMed:19838169,
CC PubMed:23234360). {ECO:0000269|PubMed:19838169,
CC ECO:0000269|PubMed:20511397, ECO:0000269|PubMed:23234360,
CC ECO:0000269|PubMed:2498325, ECO:0000303|PubMed:29516132}.
CC -!- PTM: Glycated in plasma VLDL of normal subjects, and of hyperglycemic
CC diabetic patients at a higher level (2-3 fold).
CC {ECO:0000269|PubMed:10452964}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
CC -!- PTM: Undergoes C-terminal proteolytic processing in neurons. C-
CC terminally truncated APOE has a tendency to form neurotoxic
CC intracellular neurofibrillary tangle-like inclusions in neurons.
CC {ECO:0000269|PubMed:11447277}.
CC -!- POLYMORPHISM: There are three common APOE alleles identified:
CC APOE*2/APOE-epsilon2/E2, APOE*3/APOE-epsilon3/E3, and APOE*4/APOE-
CC epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms
CC differentially present Cys and Arg residues at positions 130 and 176.
CC The most common allele in the human population is APOE*3 which sequence
CC is the one displayed in that entry with a Cys at position 130 and an
CC Arg at position 176. Common APOE variants influence lipoprotein
CC metabolism in healthy individuals. Additional variants have been
CC described and are described relative to the three common alleles.
CC Allele APOE*4 is strongly associated with risk for severe COVID-19,
CC increases susceptibility to SARS-CoV-2 infection in neurons and
CC astrocytes (PubMed:33450186). {ECO:0000269|PubMed:2987927,
CC ECO:0000269|PubMed:3243553, ECO:0000269|PubMed:33450186,
CC ECO:0000269|PubMed:6325438, ECO:0000303|PubMed:25173806}.
CC -!- DISEASE: Hyperlipoproteinemia 3 (HLPP3) [MIM:617347]: A disorder
CC characterized by the accumulation of intermediate-density lipoprotein
CC particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical
CC features include xanthomas, yellowish lipid deposits in the palmar
CC crease, or less specific on tendons and on elbows. The disorder rarely
CC manifests before the third decade in men. In women, it is usually
CC expressed only after the menopause. {ECO:0000269|PubMed:1361196,
CC ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:2101409,
CC ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2556398,
CC ECO:0000269|PubMed:26802169, ECO:0000269|PubMed:2738044,
CC ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:8287539}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. The vast majority of the patients are homozygous for APOE*2
CC alleles. More severe cases of HLPP3 have also been observed in
CC individuals heterozygous for rare APOE variants. The influence of APOE
CC on lipid levels is often suggested to have major implications for the
CC risk of coronary artery disease (CAD). Individuals carrying the common
CC APOE*4 variant are at higher risk of CAD.
CC -!- DISEASE: Alzheimer disease 2 (AD2) [MIM:104310]: A late-onset form of
CC Alzheimer disease. Alzheimer disease is a neurodegenerative disorder
CC characterized by progressive dementia, loss of cognitive abilities, and
CC deposition of fibrillar amyloid proteins as intraneuronal
CC neurofibrillary tangles, extracellular amyloid plaques and vascular
CC amyloid deposits. The major constituents of these plaques are
CC neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that
CC are produced by the proteolysis of the transmembrane APP protein. The
CC cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products,
CC such as C31, are also implicated in neuronal death.
CC {ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:11258893,
CC ECO:0000269|PubMed:11447277, ECO:0000269|PubMed:28111074,
CC ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887,
CC ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364,
CC ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470,
CC ECO:0000269|PubMed:8939961}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry. The APOE*4
CC allele (APOE form E4) is genetically associated with the common late
CC onset familial and sporadic forms of Alzheimer disease. Risk for AD
CC increased from 20% to 90% and mean age at onset decreased from 84 to 68
CC years with increasing number of APOE*4 alleles in 42 families with late
CC onset AD. Thus APOE*4 gene dose is a major risk factor for late onset
CC AD and, in these families, homozygosity for APOE*4 was virtually
CC sufficient to cause AD by age 80. The mechanism by which APOE*4
CC participates in pathogenesis is not known.
CC {ECO:0000269|PubMed:8346443}.
CC -!- DISEASE: Sea-blue histiocyte disease (SBHD) [MIM:269600]: Characterized
CC by splenomegaly, mild thrombocytopenia and, in the bone marrow,
CC numerous histiocytes containing cytoplasmic granules which stain bright
CC blue with the usual hematologic stains. The syndrome is the consequence
CC of an inherited metabolic defect analogous to Gaucher disease and other
CC sphingolipidoses. {ECO:0000269|PubMed:11095479,
CC ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068,
CC ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230,
CC ECO:0000269|PubMed:26802169}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney
CC disease characterized by proteinuria, progressive kidney failure, and
CC distinctive lipoprotein thrombi in glomerular capillaries.
CC {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:10903326,
CC ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Binds to and activates LILRB4 on acute myeloid leukemia
CC (AML) cells which leads to suppression of T cell proliferation and
CC promotion of AML cell migration and infiltration.
CC {ECO:0000269|PubMed:30333625}.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Apolipoprotein E entry;
CC URL="https://en.wikipedia.org/wiki/Apolipoprotein_E";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Tangled - Issue 83 of June
CC 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/083";
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DR EMBL; M12529; AAB59518.1; -; mRNA.
DR EMBL; K00396; AAB59546.1; -; mRNA.
DR EMBL; M10065; AAB59397.1; -; Genomic_DNA.
DR EMBL; AF050154; AAD02505.1; -; Genomic_DNA.
DR EMBL; AF261279; AAG27089.1; -; Genomic_DNA.
DR EMBL; AK314898; BAG37412.1; -; mRNA.
DR EMBL; FJ525876; ACN81314.1; -; Genomic_DNA.
DR EMBL; BC003557; AAH03557.1; -; mRNA.
DR EMBL; AB035149; BAA96080.1; -; Genomic_DNA.
DR CCDS; CCDS12647.1; -.
DR PIR; A92478; LPHUE.
DR RefSeq; NP_000032.1; NM_000041.3.
DR RefSeq; NP_001289617.1; NM_001302688.1.
DR RefSeq; NP_001289618.1; NM_001302689.1.
DR RefSeq; NP_001289619.1; NM_001302690.1.
DR RefSeq; NP_001289620.1; NM_001302691.1.
DR PDB; 1B68; X-ray; 2.00 A; A=19-209.
DR PDB; 1BZ4; X-ray; 1.85 A; A=40-183.
DR PDB; 1EA8; X-ray; 1.95 A; A=19-209.
DR PDB; 1GS9; X-ray; 1.70 A; A=19-183.
DR PDB; 1H7I; X-ray; 1.90 A; A=19-209.
DR PDB; 1LE2; X-ray; 3.00 A; A=41-184.
DR PDB; 1LE4; X-ray; 2.50 A; A=41-184.
DR PDB; 1LPE; X-ray; 2.25 A; A=41-184.
DR PDB; 1NFN; X-ray; 1.80 A; A=19-209.
DR PDB; 1NFO; X-ray; 2.00 A; A=19-209.
DR PDB; 1OEF; NMR; -; A=281-304.
DR PDB; 1OEG; NMR; -; A=285-307.
DR PDB; 1OR2; X-ray; 2.50 A; A=19-183.
DR PDB; 1OR3; X-ray; 1.73 A; A=19-183.
DR PDB; 2KC3; NMR; -; A=19-201.
DR PDB; 2KNY; NMR; -; A=147-167.
DR PDB; 2L7B; NMR; -; A=19-317.
DR PDB; 6IWB; X-ray; 2.50 A; A/C=41-186.
DR PDB; 6NCN; X-ray; 1.82 A; A=19-180.
DR PDB; 6NCO; X-ray; 1.71 A; A=19-180.
DR PDBsum; 1B68; -.
DR PDBsum; 1BZ4; -.
DR PDBsum; 1EA8; -.
DR PDBsum; 1GS9; -.
DR PDBsum; 1H7I; -.
DR PDBsum; 1LE2; -.
DR PDBsum; 1LE4; -.
DR PDBsum; 1LPE; -.
DR PDBsum; 1NFN; -.
DR PDBsum; 1NFO; -.
DR PDBsum; 1OEF; -.
DR PDBsum; 1OEG; -.
DR PDBsum; 1OR2; -.
DR PDBsum; 1OR3; -.
DR PDBsum; 2KC3; -.
DR PDBsum; 2KNY; -.
DR PDBsum; 2L7B; -.
DR PDBsum; 6IWB; -.
DR PDBsum; 6NCN; -.
DR PDBsum; 6NCO; -.
DR AlphaFoldDB; P02649; -.
DR BMRB; P02649; -.
DR SASBDB; P02649; -.
DR SMR; P02649; -.
DR BioGRID; 106845; 145.
DR DIP; DIP-1120N; -.
DR IntAct; P02649; 86.
DR MINT; P02649; -.
DR STRING; 9606.ENSP00000252486; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB00877; Sirolimus.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MoonDB; P02649; Predicted.
DR CarbonylDB; P02649; -.
DR GlyConnect; 648; 2 O-Linked glycans (5 sites).
DR GlyGen; P02649; 8 sites, 6 O-linked glycans (8 sites).
DR iPTMnet; P02649; -.
DR MetOSite; P02649; -.
DR PhosphoSitePlus; P02649; -.
DR SwissPalm; P02649; -.
DR BioMuta; APOE; -.
DR DMDM; 114039; -.
DR DOSAC-COBS-2DPAGE; P02649; -.
DR SWISS-2DPAGE; P02649; -.
DR CPTAC; non-CPTAC-1087; -.
DR EPD; P02649; -.
DR jPOST; P02649; -.
DR MassIVE; P02649; -.
DR MaxQB; P02649; -.
DR PaxDb; P02649; -.
DR PeptideAtlas; P02649; -.
DR PRIDE; P02649; -.
DR ProteomicsDB; 51537; -.
DR ABCD; P02649; 7 sequenced antibodies.
DR Antibodypedia; 3639; 1433 antibodies from 50 providers.
DR DNASU; 348; -.
DR Ensembl; ENST00000252486.9; ENSP00000252486.3; ENSG00000130203.10.
DR GeneID; 348; -.
DR KEGG; hsa:348; -.
DR MANE-Select; ENST00000252486.9; ENSP00000252486.3; NM_000041.4; NP_000032.1.
DR UCSC; uc002pab.4; human.
DR CTD; 348; -.
DR DisGeNET; 348; -.
DR GeneCards; APOE; -.
DR HGNC; HGNC:613; APOE.
DR HPA; ENSG00000130203; Group enriched (adrenal gland, liver).
DR MalaCards; APOE; -.
DR MIM; 104310; phenotype.
DR MIM; 107741; gene.
DR MIM; 269600; phenotype.
DR MIM; 611771; phenotype.
DR MIM; 617347; phenotype.
DR neXtProt; NX_P02649; -.
DR NIAGADS; ENSG00000130203; -.
DR OpenTargets; ENSG00000130203; -.
DR Orphanet; 412; Dysbetalipoproteinemia.
DR Orphanet; 329481; Lipoprotein glomerulopathy.
DR Orphanet; 238616; NON RARE IN EUROPE: Alzheimer disease.
DR Orphanet; 1648; NON RARE IN EUROPE: Dementia with Lewy body.
DR Orphanet; 406; NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia.
DR Orphanet; 158029; Sea-blue histiocytosis.
DR PharmGKB; PA55; -.
DR VEuPathDB; HostDB:ENSG00000130203; -.
DR eggNOG; ENOG502QVD6; Eukaryota.
DR GeneTree; ENSGT00950000182929; -.
DR HOGENOM; CLU_066029_0_0_1; -.
DR InParanoid; P02649; -.
DR OMA; WFEPLVQ; -.
DR OrthoDB; 331262at2759; -.
DR PhylomeDB; P02649; -.
DR TreeFam; TF334458; -.
DR PathwayCommons; P02649; -.
DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-HSA-3000480; Scavenging by Class A Receptors.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8864260; Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-8963888; Chylomicron assembly.
DR Reactome; R-HSA-8963901; Chylomicron remodeling.
DR Reactome; R-HSA-8964026; Chylomicron clearance.
DR Reactome; R-HSA-8964058; HDL remodeling.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P02649; -.
DR SIGNOR; P02649; -.
DR BioGRID-ORCS; 348; 17 hits in 1087 CRISPR screens.
DR ChiTaRS; APOE; human.
DR EvolutionaryTrace; P02649; -.
DR GeneWiki; Apolipoprotein_E; -.
DR GenomeRNAi; 348; -.
DR Pharos; P02649; Tbio.
DR PRO; PR:P02649; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P02649; protein.
DR Bgee; ENSG00000130203; Expressed in right adrenal gland cortex and 177 other tissues.
DR ExpressionAtlas; P02649; baseline and differential.
DR Genevisible; P02649; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0042627; C:chylomicron; IDA:BHF-UCL.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0030425; C:dendrite; NAS:BHF-UCL.
DR GO; GO:0034365; C:discoidal high-density lipoprotein particle; TAS:ARUK-UCL.
DR GO; GO:0005769; C:early endosome; TAS:Reactome.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:AgBase.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:ARUK-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; IDA:AgBase.
DR GO; GO:0034364; C:high-density lipoprotein particle; IDA:UniProtKB.
DR GO; GO:0034363; C:intermediate-density lipoprotein particle; IDA:UniProtKB.
DR GO; GO:1990777; C:lipoprotein particle; IDA:ARUK-UCL.
DR GO; GO:0034362; C:low-density lipoprotein particle; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; NAS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043083; C:synaptic cleft; IDA:SynGO.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:UniProtKB.
DR GO; GO:0016209; F:antioxidant activity; IDA:BHF-UCL.
DR GO; GO:0120020; F:cholesterol transfer activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR GO; GO:0005319; F:lipid transporter activity; IDA:BHF-UCL.
DR GO; GO:0071813; F:lipoprotein particle binding; IEA:Ensembl.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:UniProtKB.
DR GO; GO:0046911; F:metal chelating activity; IDA:BHF-UCL.
DR GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IDA:BHF-UCL.
DR GO; GO:0005543; F:phospholipid binding; IDA:BHF-UCL.
DR GO; GO:0046983; F:protein dimerization activity; IPI:ARUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR GO; GO:0005198; F:structural molecule activity; TAS:ARUK-UCL.
DR GO; GO:0048156; F:tau protein binding; IPI:BHF-UCL.
DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; IDA:BHF-UCL.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; IDA:UniProtKB.
DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:BHF-UCL.
DR GO; GO:0006707; P:cholesterol catabolic process; IBA:GO_Central.
DR GO; GO:0033344; P:cholesterol efflux; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:BHF-UCL.
DR GO; GO:0034382; P:chylomicron remnant clearance; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0055089; P:fatty acid homeostasis; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0034380; P:high-density lipoprotein particle assembly; IDA:UniProtKB.
DR GO; GO:0034384; P:high-density lipoprotein particle clearance; IDA:BHF-UCL.
DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; IGI:BHF-UCL.
DR GO; GO:0071831; P:intermediate-density lipoprotein particle clearance; IDA:UniProtKB.
DR GO; GO:0046907; P:intracellular transport; TAS:UniProtKB.
DR GO; GO:0010877; P:lipid transport involved in lipid storage; ISS:BHF-UCL.
DR GO; GO:0042158; P:lipoprotein biosynthetic process; IDA:UniProtKB.
DR GO; GO:0042159; P:lipoprotein catabolic process; IBA:GO_Central.
DR GO; GO:0035641; P:locomotory exploration behavior; IMP:ARUK-UCL.
DR GO; GO:0015909; P:long-chain fatty acid transport; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0007616; P:long-term memory; IGI:ARUK-UCL.
DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IEA:Ensembl.
DR GO; GO:0051651; P:maintenance of location in cell; IEA:Ensembl.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISS:UniProtKB.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:BHF-UCL.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0090370; P:negative regulation of cholesterol efflux; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0061000; P:negative regulation of dendritic spine development; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IMP:ARUK-UCL.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0051055; P:negative regulation of lipid biosynthetic process; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1903001; P:negative regulation of lipid transport across blood-brain barrier; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IDA:ARUK-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IBA:GO_Central.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:ARUK-UCL.
DR GO; GO:1902999; P:negative regulation of phospholipid efflux; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0010544; P:negative regulation of platelet activation; IDA:BHF-UCL.
DR GO; GO:1901627; P:negative regulation of postsynaptic membrane organization; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; IGI:ARUK-UCL.
DR GO; GO:0050709; P:negative regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISS:BHF-UCL.
DR GO; GO:0090209; P:negative regulation of triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IDA:BHF-UCL.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0033700; P:phospholipid efflux; IDA:BHF-UCL.
DR GO; GO:0044794; P:positive regulation by host of viral process; IMP:AgBase.
DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; TAS:ARUK-UCL.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:UniProtKB.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IDA:BHF-UCL.
DR GO; GO:1905920; P:positive regulation of CoA-transferase activity; IDA:BHF-UCL.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0045807; P:positive regulation of endocytosis; IDA:ARUK-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:1905855; P:positive regulation of heparan sulfate binding; IDA:ARUK-UCL.
DR GO; GO:1905860; P:positive regulation of heparan sulfate proteoglycan binding; IDA:ARUK-UCL.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1903002; P:positive regulation of lipid transport across blood-brain barrier; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; IDA:BHF-UCL.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL.
DR GO; GO:1902998; P:positive regulation of neurofibrillary tangle assembly; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1901216; P:positive regulation of neuron death; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:ARUK-UCL.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IDA:BHF-UCL.
DR GO; GO:1902995; P:positive regulation of phospholipid efflux; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:1901631; P:positive regulation of presynaptic membrane organization; IDA:ARUK-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0017038; P:protein import; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:BHF-UCL.
DR GO; GO:1905906; P:regulation of amyloid fibril formation; IDA:ARUK-UCL.
DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; IDA:UniProtKB.
DR GO; GO:1900221; P:regulation of amyloid-beta clearance; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0030516; P:regulation of axon extension; TAS:UniProtKB.
DR GO; GO:2000822; P:regulation of behavioral fear response; IMP:ARUK-UCL.
DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IDA:BHF-UCL.
DR GO; GO:1905890; P:regulation of cellular response to very-low-density lipoprotein particle stimulus; IDA:ARUK-UCL.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IGI:ARUK-UCL.
DR GO; GO:0045088; P:regulation of innate immune response; IEA:Ensembl.
DR GO; GO:1901214; P:regulation of neuron death; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; TAS:UniProtKB.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0051246; P:regulation of protein metabolic process; IGI:ARUK-UCL.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:ARUK-UCL.
DR GO; GO:1902947; P:regulation of tau-protein kinase activity; IDA:Alzheimers_University_of_Toronto.
DR GO; GO:0061771; P:response to caloric restriction; IGI:ARUK-UCL.
DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
DR GO; GO:0000302; P:response to reactive oxygen species; NAS:UniProtKB.
DR GO; GO:0043691; P:reverse cholesterol transport; IDA:BHF-UCL.
DR GO; GO:0007271; P:synaptic transmission, cholinergic; TAS:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; ISS:BHF-UCL.
DR GO; GO:0006641; P:triglyceride metabolic process; IDA:BHF-UCL.
DR GO; GO:0071830; P:triglyceride-rich lipoprotein particle clearance; IMP:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; IDA:UniProtKB.
DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IDA:BHF-UCL.
DR GO; GO:0019068; P:virion assembly; IMP:AgBase.
DR InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alzheimer disease; Amyloidosis; Cholesterol metabolism;
KW Chylomicron; Direct protein sequencing; Disease variant;
KW Extracellular matrix; Glycation; Glycoprotein; HDL; Heparin-binding;
KW Host-virus interaction; Hyperlipidemia; Lipid metabolism; Lipid transport;
KW Lipid-binding; Neurodegeneration; Oxidation; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal; Steroid metabolism;
KW Sterol metabolism; Transport; VLDL.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:7068630"
FT CHAIN 19..317
FT /note="Apolipoprotein E"
FT /id="PRO_0000001987"
FT REPEAT 80..101
FT /note="1"
FT REPEAT 102..123
FT /note="2"
FT REPEAT 124..145
FT /note="3"
FT REPEAT 146..167
FT /note="4"
FT REPEAT 168..189
FT /note="5"
FT REPEAT 190..211
FT /note="6"
FT REPEAT 212..233
FT /note="7"
FT REPEAT 234..255
FT /note="8"
FT REGION 80..255
FT /note="8 X 22 AA approximate tandem repeats"
FT REGION 158..168
FT /note="LDL and other lipoprotein receptors binding"
FT /evidence="ECO:0000269|PubMed:20030366,
FT ECO:0000269|PubMed:2063194"
FT REGION 210..290
FT /note="Lipid-binding and lipoprotein association"
FT /evidence="ECO:0000269|PubMed:2280190,
FT ECO:0000269|PubMed:8071364"
FT REGION 266..317
FT /note="Homooligomerization"
FT /evidence="ECO:0000269|PubMed:8340399"
FT REGION 278..290
FT /note="Specificity for association with VLDL"
FT /evidence="ECO:0000269|PubMed:8071364"
FT BINDING 162..165
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000269|PubMed:3947350"
FT BINDING 229..236
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000269|PubMed:3947350"
FT MOD_RES 143
FT /note="Methionine sulfoxide"
FT /evidence="ECO:0000250|UniProtKB:P08226"
FT MOD_RES 147
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039,
FT ECO:0007744|PubMed:24275569"
FT CARBOHYD 26
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 36
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 93
FT /note="N-linked (Glc) (glycation) lysine"
FT /evidence="ECO:0000269|PubMed:10452964"
FT CARBOHYD 212
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19838169,
FT ECO:0000269|PubMed:2498325"
FT CARBOHYD 307
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19838169"
FT CARBOHYD 308
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:19838169,
FT ECO:0000269|PubMed:20511397"
FT CARBOHYD 314
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT VARIANT 21
FT /note="E -> K (in ApoE5; associated with
FT hyperlipoproteinemia and atherosclerosis; increased binding
FT to LDL receptor; dbSNP:rs121918392)"
FT /evidence="ECO:0000269|PubMed:1530612,
FT ECO:0000269|PubMed:2760009"
FT /id="VAR_000645"
FT VARIANT 31
FT /note="E -> K (in HLPP3; ApoE4 Philadelphia, ApoE5 French-
FT Canadian and ApoE5-type; only ApoE4 Philadelphia is
FT associated with HLPP3; dbSNP:rs201672011)"
FT /evidence="ECO:0000269|PubMed:1674745,
FT ECO:0000269|PubMed:1713245, ECO:0000303|PubMed:7833947"
FT /id="VAR_000646"
FT VARIANT 43
FT /note="R -> C (in LPG; ApoE2 Kyoto; dbSNP:rs121918399)"
FT /evidence="ECO:0000269|PubMed:10432380,
FT ECO:0000269|PubMed:18077821"
FT /id="VAR_042734"
FT VARIANT 46
FT /note="L -> P (found in a patient with
FT hypercholesterolemia; unknown pathological significance;
FT ApoE4 Freiburg; dbSNP:rs769452)"
FT /evidence="ECO:0000269|PubMed:11042151,
FT ECO:0000269|PubMed:26802169"
FT /id="VAR_000647"
FT VARIANT 60
FT /note="T -> A (in ApoE3 Freiburg; dbSNP:rs28931576)"
FT /id="VAR_000648"
FT VARIANT 64
FT /note="Q -> H (confirmed at protein level;
FT dbSNP:rs370594287)"
FT /evidence="ECO:0000269|PubMed:22028381, ECO:0000269|Ref.10"
FT /id="VAR_014114"
FT VARIANT 99
FT /note="Q -> K (in ApoE5 Frankfurt; dbSNP:rs1180612218)"
FT /evidence="ECO:0000269|PubMed:8125051"
FT /id="VAR_000649"
FT VARIANT 102
FT /note="P -> R (in ApoE5-type; no hyperlipidemia;
FT dbSNP:rs11083750)"
FT /evidence="ECO:0000303|PubMed:7833947"
FT /id="VAR_000650"
FT VARIANT 117
FT /note="A -> T (in ApoE3*; dbSNP:rs28931577)"
FT /evidence="ECO:0000269|PubMed:6327682"
FT /id="VAR_000651"
FT VARIANT 124
FT /note="A -> V (in ApoE3 Basel; dbSNP:rs937063425)"
FT /evidence="ECO:0000269|PubMed:12864777"
FT /id="VAR_016789"
FT VARIANT 130
FT /note="C -> R (in HLPP3 and AD2; ApoE4, ApoE3 Leiden,
FT ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and
FT ApoE3** are associated with HLPP3; ApoE4 is associated with
FT AD2; changed protein structure; no effect on binding to LDL
FT receptor; decreased association with HDL and enrichment in
FT VLDL and IDL; may prevent the interaction with MAP2 and
FT MAPT; changed interaction with APP/A4 amyloid-beta peptide;
FT increased ability to induce APP transcription; increased C-
FT terminal proteolytic processing in neurons; decreased
FT function in neurite outgrowth; ApoE4 is associated with
FT higher susceptibility to SARS-CoV-2 infection in neurons
FT and astrocytes; dbSNP:rs429358)"
FT /evidence="ECO:0000269|PubMed:10903326,
FT ECO:0000269|PubMed:11042151, ECO:0000269|PubMed:11447277,
FT ECO:0000269|PubMed:12966036, ECO:0000269|PubMed:2280190,
FT ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:28111074,
FT ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887,
FT ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364,
FT ECO:0000269|PubMed:8125051, ECO:0000269|PubMed:8287539,
FT ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470,
FT ECO:0000269|PubMed:8939961, ECO:0000269|PubMed:9360638,
FT ECO:0000303|PubMed:7833947"
FT /id="VAR_000652"
FT VARIANT 145
FT /note="G -> D (found in a patient with
FT hypercholesterolemia; unknown pathological significance;
FT ApoE1 Weisgraber; dbSNP:rs267606664)"
FT /evidence="ECO:0000269|PubMed:26802169,
FT ECO:0000269|PubMed:8287539"
FT /id="VAR_000653"
FT VARIANT 145
FT /note="G -> GEVQAMLG (in HLPP3; ApoE3 Leiden; no effect on
FT glycosylation)"
FT /evidence="ECO:0000269|PubMed:2556398,
FT ECO:0000269|PubMed:8468528"
FT /id="VAR_000654"
FT VARIANT 152
FT /note="R -> Q (in ApoE2-type; no hyperlipidemia;
FT dbSNP:rs28931578)"
FT /evidence="ECO:0000303|PubMed:7833947"
FT /id="VAR_000655"
FT VARIANT 154
FT /note="R -> C (in HLPP3; ApoE2-type; dbSNP:rs121918393)"
FT /evidence="ECO:0000303|PubMed:7833947"
FT /id="VAR_000657"
FT VARIANT 154
FT /note="R -> S (in HLPP3; ApoE2 Christchurch; decreased
FT binding to LDL receptor; dbSNP:rs121918393)"
FT /evidence="ECO:0000269|PubMed:22481068,
FT ECO:0000269|PubMed:2831187, ECO:0000269|PubMed:8287539"
FT /id="VAR_000656"
FT VARIANT 160
FT /note="R -> C (in HLPP3; ApoE3**; dbSNP:rs387906567)"
FT /evidence="ECO:0000269|PubMed:8287539"
FT /id="VAR_000658"
FT VARIANT 163
FT /note="R -> C (in HLPP3; also found in a patient with
FT hypercholesterolemia; ApoE4 Philadelphia and ApoE2-type;
FT dbSNP:rs769455)"
FT /evidence="ECO:0000269|PubMed:11042151,
FT ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:26802169"
FT /id="VAR_000659"
FT VARIANT 163
FT /note="R -> H (in HLPP3; unknown pathological significance;
FT ApoE Kochi; dbSNP:rs121918397)"
FT /evidence="ECO:0000269|PubMed:2101409"
FT /id="VAR_000660"
FT VARIANT 163
FT /note="R -> P (in LPG; ApoE2 Sendai; decreased binding to
FT LDL receptor; induces intraglomerular deposition of ApoE-
FT containing lipoproteins; dbSNP:rs121918397)"
FT /evidence="ECO:0000269|PubMed:10903326,
FT ECO:0000269|PubMed:9176854"
FT /id="VAR_042735"
FT VARIANT 164
FT /note="K -> E (in HLPP3; ApoE1 Harrisburg; decreased
FT binding to LDL receptor; probable dominant negative effect;
FT decreased in vitro binding to heparin; dbSNP:rs121918394)"
FT /evidence="ECO:0000269|PubMed:7635945"
FT /id="VAR_000662"
FT VARIANT 164
FT /note="K -> Q (in HLPP3; ApoE2**; dbSNP:rs121918394)"
FT /id="VAR_000661"
FT VARIANT 167
FT /note="Missing (in SBHD; also found in patients with a
FT diagnosis of familial combined hyperlipidemia)"
FT /evidence="ECO:0000269|PubMed:11095479,
FT ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068,
FT ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230,
FT ECO:0000269|PubMed:26802169"
FT /id="VAR_035015"
FT VARIANT 170
FT /note="A -> P (in ApoE3*; decreased binding to LDL
FT receptor; dbSNP:rs267606662)"
FT /evidence="ECO:0000269|PubMed:2831187,
FT ECO:0000269|PubMed:6327682"
FT /id="VAR_000663"
FT VARIANT 176
FT /note="R -> C (in HLPP3; ApoE2, ApoE2 Fukuoka, ApoE1
FT Weisgraber and ApoE3**; ApoE3** is associated with HLPP3;
FT changed protein structure; decreased binding to LDLR and
FT other lipoprotein receptors; decreased in vitro binding to
FT heparin; no effect on distribution among plasma
FT lipoproteins; dbSNP:rs7412)"
FT /evidence="ECO:0000269|PubMed:11042151,
FT ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:12966036,
FT ECO:0000269|PubMed:2280190, ECO:0000269|PubMed:3243553,
FT ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7994571,
FT ECO:0000269|PubMed:8287539, ECO:0000269|PubMed:8756331"
FT /id="VAR_000664"
FT VARIANT 228..317
FT /note="Missing (in HLPP3; ApoE3 Washington)"
FT /evidence="ECO:0000269|PubMed:1361196"
FT /id="VAR_081136"
FT VARIANT 242
FT /note="R -> Q (in ApoE2 Fukuoka; dbSNP:rs267606663)"
FT /evidence="ECO:0000269|PubMed:8664327"
FT /id="VAR_000665"
FT VARIANT 246
FT /note="R -> C (in ApoE2 Dunedin; dbSNP:rs121918395)"
FT /evidence="ECO:0000269|PubMed:2341812"
FT /id="VAR_000666"
FT VARIANT 254
FT /note="V -> E (in ApoE2 WG; dbSNP:rs199768005)"
FT /evidence="ECO:0000269|PubMed:8488843"
FT /id="VAR_000667"
FT VARIANT 262..263
FT /note="EE -> KK (in HLPP3; ApoE7 Suita)"
FT /evidence="ECO:0000269|PubMed:2738044"
FT /id="VAR_000668"
FT VARIANT 269
FT /note="R -> G (in ApoE3 HB; dbSNP:rs267606661)"
FT /evidence="ECO:0000269|PubMed:8488843,
FT ECO:0000269|PubMed:9360638"
FT /id="VAR_000669"
FT VARIANT 270
FT /note="L -> E (in ApoE1 HE; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:8488843"
FT /id="VAR_000670"
FT VARIANT 292
FT /note="R -> H (in ApoE4 PD; dbSNP:rs121918398)"
FT /evidence="ECO:0000269|PubMed:8488843"
FT /id="VAR_000671"
FT VARIANT 314
FT /note="S -> R (in ApoE4 HG; dbSNP:rs28931579)"
FT /evidence="ECO:0000269|PubMed:8488843"
FT /id="VAR_000672"
FT MUTAGEN 79
FT /note="R->T: Changes the plasma lipoprotein distribution of
FT ApoE4 to the HDL."
FT /evidence="ECO:0000269|PubMed:8071364"
FT MUTAGEN 127
FT /note="E->A: No effect on plasma lipoprotein distribution."
FT /evidence="ECO:0000269|PubMed:8071364"
FT MUTAGEN 157
FT /note="S->R: Increased binding to LDL receptor; when
FT associated with A-167."
FT /evidence="ECO:0000269|PubMed:2831187"
FT MUTAGEN 158
FT /note="H->A: Decreased binding to LDL receptor."
FT /evidence="ECO:0000269|PubMed:2831187"
FT MUTAGEN 161
FT /note="K->A: Decreased binding to LDL receptor."
FT /evidence="ECO:0000269|PubMed:2831187"
FT MUTAGEN 162
FT /note="L->P: Decreased binding to LDL receptor."
FT /evidence="ECO:0000269|PubMed:2831187"
FT MUTAGEN 167
FT /note="L->A: Increased binding to LDL receptor; when
FT associated with R-157."
FT /evidence="ECO:0000269|PubMed:2831187"
FT MUTAGEN 168
FT /note="R->A: Decreased binding to LDL receptor."
FT /evidence="ECO:0000269|PubMed:2831187"
FT MUTAGEN 172
FT /note="D->A: Restores the LDL receptor binding activity of
FT ApoE2."
FT /evidence="ECO:0000269|PubMed:8756331"
FT MUTAGEN 212
FT /note="T->A: Loss of O-glycosylation."
FT /evidence="ECO:0000269|PubMed:2498325"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2KC3"
FT HELIX 31..39
FT /evidence="ECO:0007829|PDB:2KC3"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:2KC3"
FT HELIX 43..60
FT /evidence="ECO:0007829|PDB:1GS9"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:1GS9"
FT HELIX 73..96
FT /evidence="ECO:0007829|PDB:1GS9"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:1LE4"
FT HELIX 106..141
FT /evidence="ECO:0007829|PDB:1GS9"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:6NCO"
FT HELIX 149..179
FT /evidence="ECO:0007829|PDB:1GS9"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:1BZ4"
FT TURN 187..190
FT /evidence="ECO:0007829|PDB:2KC3"
FT HELIX 193..198
FT /evidence="ECO:0007829|PDB:2KC3"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:2L7B"
FT HELIX 209..217
FT /evidence="ECO:0007829|PDB:2L7B"
FT HELIX 228..241
FT /evidence="ECO:0007829|PDB:2L7B"
FT HELIX 257..283
FT /evidence="ECO:0007829|PDB:2L7B"
FT HELIX 286..303
FT /evidence="ECO:0007829|PDB:1OEF"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:2L7B"
SQ SEQUENCE 317 AA; 36154 MW; 91AFC04210A30689 CRC64;
MKVLWAALLV TFLAGCQAKV EQAVETEPEP ELRQQTEWQS GQRWELALGR FWDYLRWVQT
LSEQVQEELL SSQVTQELRA LMDETMKELK AYKSELEEQL TPVAEETRAR LSKELQAAQA
RLGADMEDVC GRLVQYRGEV QAMLGQSTEE LRVRLASHLR KLRKRLLRDA DDLQKRLAVY
QAGAREGAER GLSAIRERLG PLVEQGRVRA ATVGSLAGQP LQERAQAWGE RLRARMEEMG
SRTRDRLDEV KEQVAEVRAK LEEQAQQIRL QAEAFQARLK SWFEPLVEDM QRQWAGLVEK
VQAAVGTSAA PVPSDNH
