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 02-OCT-2024, entry version 273. 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 SUBCELLULAR LOCATION, AND INTERACTION WITH PMEL. RX PubMed=26387950; DOI=10.1016/j.celrep.2015.08.057; RA van Niel G., Bergam P., Di Cicco A., Hurbain I., Lo Cicero A., Dingli F., RA Palmulli R., Fort C., Potier M.C., Schurgers L.J., Loew D., Levy D., RA Raposo G.; RT "Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment RT Cells."; RL Cell Rep. 13:43-51(2015). RN [49] 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 [50] 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 [51] 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 [52] {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 [53] {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 [54] {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 [55] {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 [56] {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 [57] {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 [58] {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 [59] 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 [60] 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 [61] 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 [62] 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 [63] 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 [64] 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 [65] 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 [66] 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 [67] 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 [68] 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 [69] 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 [70] 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 [71] 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 [72] 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 [73] 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 [74] 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 [75] 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 [76] 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 [77] 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 [78] 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 [79] 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 [80] 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 [81] 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 [82] 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 [83] 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 [84] 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 [85] 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 [86] 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 [87] 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 [88] 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 [89] 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 [90] 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 [91] 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 [92] 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:14754908, PubMed:1911868, PubMed:6860692). APOE is a core CC component of plasma lipoproteins and is involved in their production, CC conversion and clearance (PubMed:14754908, PubMed:1911868, CC PubMed:1917954, PubMed:23620513, PubMed:2762297, PubMed:6860692, CC PubMed:9395455). Apolipoproteins are amphipathic molecules that CC interact both with lipids of the lipoprotein particle core and the CC aqueous environment of the plasma (PubMed:2762297, PubMed:6860692, 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:1911868, CC PubMed:6860692). 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:12950167, PubMed:1530612, PubMed:1917954, CC PubMed:20030366, PubMed:20303980, PubMed:2063194, PubMed:2762297, CC PubMed:7635945, PubMed:7768901, PubMed:8756331, PubMed:8939961). 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:23676495, PubMed:7635945, PubMed:9395455, CC PubMed:9488694). 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:23676495, CC PubMed:29516132, PubMed:9395455). 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:1917954, PubMed:2762297, 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:14754908, PubMed:23620513, CC PubMed:9395455). First, it is functionally associated with ABCA1 in the CC 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:25173806, PubMed:8939961). 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:23620513, PubMed:8367470). 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). Interacts with PMEL; this allows the loading of PMEL CC luminal fragment on ILVs to induce fibril nucleation. CC {ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:23620513, CC ECO:0000269|PubMed:26387950, 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; Q9NUB4: C20orf141; NbExp=3; IntAct=EBI-1222467, EBI-9088162; CC P02649; P02748: C9; NbExp=2; IntAct=EBI-1222467, EBI-6677628; 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; Q9H6J7-2: CSTPP1; NbExp=3; IntAct=EBI-1222467, EBI-13328871; 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; P21796: VDAC1; NbExp=2; IntAct=EBI-1222467, EBI-354158; 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}. Extracellular CC vesicle {ECO:0000269|PubMed:26387950}. Endosome, multivesicular body CC {ECO:0000269|PubMed:26387950}. Note=In the plasma, APOE is associated CC with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL CC lipoproteins (PubMed:1911868, PubMed:8340399). Lipid poor oligomeric CC APOE is associated with the extracellular matrix in a calcium- and CC heparan-sulfate proteoglycans-dependent manner (PubMed:9488694). CC Lipidation induces the release from the extracellular matrix CC (PubMed:9488694). Colocalizes with CD63 and PMEL at exosomes and in CC intraluminal vesicles within multivesicular endosomes. CC {ECO:0000269|PubMed:1911868, ECO:0000269|PubMed:26387950, 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:10027417, PubMed:3115992). 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:19838169, CC PubMed:20511397, PubMed:23234360, PubMed:2498325). Glycosylation is not CC 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7FCR; X-ray; 1.40 A; A=19-209. DR PDB; 7FCS; X-ray; 1.60 A; A=19-209. DR PDB; 7UVJ; X-ray; 1.99 A; A/B=40-183. DR PDB; 8AX8; X-ray; 1.55 A; A=19-317. DR PDB; 8AX9; X-ray; 1.55 A; A=19-317. DR PDB; 8CDY; X-ray; 1.90 A; A=19-317. DR PDB; 8CE0; X-ray; 1.75 A; A=19-317. DR PDB; 8GRX; EM; 3.00 A; A/C=41-180. 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 PDBsum; 7FCR; -. DR PDBsum; 7FCS; -. DR PDBsum; 7UVJ; -. DR PDBsum; 8AX8; -. DR PDBsum; 8AX9; -. DR PDBsum; 8CDY; -. DR PDBsum; 8CE0; -. DR PDBsum; 8GRX; -. DR AlphaFoldDB; P02649; -. DR BMRB; P02649; -. DR EMDB; EMD-34216; -. DR SASBDB; P02649; -. DR SMR; P02649; -. DR BioGRID; 106845; 154. DR DIP; DIP-1120N; -. DR IntAct; P02649; 95. 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 TCDB; 9.B.445.2.1; the apolipoprotein a2 (alp-a2) family. DR CarbonylDB; P02649; -. DR GlyConnect; 648; 2 O-Linked glycans (5 sites). DR GlyCosmos; P02649; 8 sites, 5 glycans. DR GlyGen; P02649; 8 sites, 7 O-linked glycans (8 sites). DR iPTMnet; P02649; -. DR MetOSite; P02649; -. DR PhosphoSitePlus; P02649; -. DR SwissPalm; P02649; -. DR BioMuta; APOE; -. DR DMDM; 114039; -. DR CPTAC; non-CPTAC-1087; -. DR jPOST; P02649; -. DR MassIVE; P02649; -. DR PaxDb; 9606-ENSP00000252486; -. DR PeptideAtlas; P02649; -. DR ProteomicsDB; 51537; -. DR Pumba; P02649; -. DR ABCD; P02649; 7 sequenced antibodies. DR Antibodypedia; 3639; 1551 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 AGR; HGNC:613; -. DR CTD; 348; -. DR DisGeNET; 348; -. DR GeneCards; APOE; -. DR HGNC; HGNC:613; APOE. DR HPA; ENSG00000130203; Group enriched (adrenal gland, brain, 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; 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; GHMTDAR; -. DR OrthoDB; 4591103at2759; -. 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; 20 hits in 1163 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 179 other cell types or tissues. DR ExpressionAtlas; P02649; baseline and differential. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0042627; C:chylomicron; IDA:BHF-UCL. DR GO; GO:0034360; C:chylomicron remnant; IDA:ARUK-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; IDA: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:0042470; C:melanosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0097487; C:multivesicular body, internal vesicle; IDA: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; IBA:GO_Central. 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; IPI:ARUK-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IDA:ARUK-UCL. DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProt. 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:0055090; P:acylglycerol homeostasis; IBA:GO_Central. 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:0071402; P:cellular response to lipoprotein particle stimulus; IDA:UniProt. DR GO; GO:0006707; P:cholesterol catabolic process; IEA:Ensembl. 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:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl. 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; IEA:Ensembl. 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:0032438; P:melanosome organization; IMP:UniProtKB. 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: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: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:0010977; P:negative regulation of neuron projection development; IDA:ARUK-UCL. DR GO; GO:0010544; P:negative regulation of platelet activation; IDA:BHF-UCL. 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:0038060; P:nitric oxide-cGMP-mediated signaling; 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: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:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. 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: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:0010976; P:positive regulation of neuron projection development; IDA:ARUK-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL. DR GO; GO:1902995; P:positive regulation of phospholipid efflux; IDA:Alzheimers_University_of_Toronto. 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:0042981; P:regulation of apoptotic process; IEA:Ensembl. 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: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: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 Gene3D; 1.20.120.20; Apolipoprotein; 2. DR InterPro; IPR000074; ApoA_E. DR InterPro; IPR050163; Apolipoprotein_A1/A4/E. DR PANTHER; PTHR18976; APOLIPOPROTEIN; 1. DR PANTHER; PTHR18976:SF2; APOLIPOPROTEIN E; 1. DR Pfam; PF01442; Apolipoprotein; 1. DR SUPFAM; SSF58113; Apolipoprotein A-I; 1. PE 1: Evidence at protein level; KW 3D-structure; Alzheimer disease; Amyloidosis; Cholesterol metabolism; KW Chylomicron; Direct protein sequencing; Disease variant; Endosome; KW Extracellular matrix; Glycation; Glycoprotein; HDL; Heparin-binding; KW Host-virus interaction; Hyperlipidemia; Lipid metabolism; Lipid transport; KW Lipid-binding; Neurodegeneration; Oxidation; Phosphoprotein; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal; KW Steroid metabolism; 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; uncertain significance; ApoE4 FT 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; uncertain significance; ApoE1 FT 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; uncertain significance; ApoE FT 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:7FCR" FT HELIX 63..70 FT /evidence="ECO:0007829|PDB:7FCR" FT HELIX 73..96 FT /evidence="ECO:0007829|PDB:7FCR" FT HELIX 97..99 FT /evidence="ECO:0007829|PDB:7FCR" FT STRAND 103..105 FT /evidence="ECO:0007829|PDB:7UVJ" FT HELIX 107..142 FT /evidence="ECO:0007829|PDB:7FCR" FT TURN 143..145 FT /evidence="ECO:0007829|PDB:7FCR" FT HELIX 149..180 FT /evidence="ECO:0007829|PDB:7FCR" 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 //