ID APOE_MOUSE Reviewed; 311 AA. AC P08226; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 2. DT 27-MAR-2024, entry version 213. DE RecName: Full=Apolipoprotein E; DE Short=Apo-E; DE Flags: Precursor; GN Name=Apoe; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2550421; DOI=10.1093/oxfordjournals.jbchem.a122828; RA Horiuchi K., Tajima S., Menju M., Yamamoto A.; RT "Structure and expression of mouse apolipoprotein E gene."; RL J. Biochem. 106:98-103(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3865219; DOI=10.1073/pnas.82.23.8085; RA Rajavashisth T.B., Kaptein J.S., Reue K.L., Lusis A.J.; RT "Evolution of apolipoprotein E: mouse sequence and evidence for an 11- RT nucleotide ancestral unit."; RL Proc. Natl. Acad. Sci. U.S.A. 82:8085-8089(1985). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-311. RX PubMed=1870200; DOI=10.1128/jvi.65.9.4759-4768.1991; RA Diedrich J.F., Minnigan M., Carp R.I., Whitaker J.N., Race R., Frey W. II, RA Haase A.T.; RT "Neuropathological changes in scrapie and Alzheimer's disease are RT associated with increased expression of apolipoprotein E and cathepsin D in RT astrocytes."; RL J. Virol. 65:4759-4768(1991). RN [5] RP PROTEIN SEQUENCE OF 43-48; 87-100; 114-122; 130-144; 183-188; 191-198; RP 202-214; 226-236 AND 253-284, IDENTIFICATION BY MASS SPECTROMETRY, AND RP OXIDATION AT MET-135. RX PubMed=16876491; DOI=10.1016/j.bbapap.2006.06.001; RA Puppione D.L., Yam L.M., Bassilian S., Souda P., Castellani L.W., RA Schumaker V.N., Whitelegge J.P.; RT "Mass spectral analysis of the apolipoproteins on mouse high density RT lipoproteins. Detection of post-translational modifications."; RL Biochim. Biophys. Acta 1764:1363-1371(2006). RN [6] RP PROTEIN SEQUENCE OF 114-122, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP DISRUPTION PHENOTYPE. RX PubMed=1423598; DOI=10.1016/0092-8674(92)90362-g; RA Plump A.S., Smith J.D., Hayek T., Aalto-Setaelae K., Walsh A., RA Verstuyft J.G., Rubin E.M., Breslow J.L.; RT "Severe hypercholesterolemia and atherosclerosis in apolipoprotein E- RT deficient mice created by homologous recombination in ES cells."; RL Cell 71:343-353(1992). RN [9] RP DISRUPTION PHENOTYPE. RX PubMed=12569158; DOI=10.1172/jci15555; RA Lesnik P., Haskell C.A., Charo I.F.; RT "Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine RT in atherogenesis."; RL J. Clin. Invest. 111:333-340(2003). RN [10] RP DISRUPTION PHENOTYPE. RX PubMed=20037584; DOI=10.1038/ni.1836; RA Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., RA Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A., RA El Khoury J., Golenbock D.T., Moore K.J.; RT "CD36 ligands promote sterile inflammation through assembly of a Toll-like RT receptor 4 and 6 heterodimer."; RL Nat. Immunol. 11:155-161(2010). RN [11] RP FUNCTION - IN LIPOPROTEIN CLEARANCE VIA HEPARAN, AND HEPARAN-SULFATE RP PROTEOGLYCANS 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 [12] RP DISRUPTION PHENOTYPE. RX PubMed=23812099; DOI=10.1038/ni.2639; RA Sheedy F.J., Grebe A., Rayner K.J., Kalantari P., Ramkhelawon B., RA Carpenter S.B., Becker C.E., Ediriweera H.N., Mullick A.E., Golenbock D.T., RA Stuart L.M., Latz E., Fitzgerald K.A., Moore K.J.; RT "CD36 coordinates NLRP3 inflammasome activation by facilitating RT intracellular nucleation of soluble ligands into particulate ligands in RT sterile inflammation."; RL Nat. Immunol. 14:812-820(2013). RN [13] RP DISRUPTION PHENOTYPE. 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 [14] RP GLYCOSYLATION. 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). 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. APOE CC is a core component of plasma lipoproteins and is involved in their CC production, conversion and clearance. Apolipoproteins are amphipathic CC molecules that interact both with lipids of the lipoprotein particle CC core and the aqueous environment of the plasma. As such, APOE CC associates with chylomicrons, chylomicron remnants, very low density CC lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but CC shows a preferential binding to high-density lipoproteins (HDL). It CC also binds a wide range of cellular receptors including the LDL CC receptor/LDLR and the very low-density lipoprotein receptor/VLDLR that CC mediate the cellular uptake of the APOE-containing lipoprotein CC particles (By similarity). Finally, APOE has also a heparin-binding CC activity and binds heparan-sulfate proteoglycans on the surface of CC cells, a property that supports the capture and the receptor-mediated CC uptake of APOE-containing lipoproteins by cells (PubMed:23676495). CC {ECO:0000250|UniProtKB:P02649, ECO:0000269|PubMed:23676495}. CC -!- SUBUNIT: Homotetramer. May interact with ABCA1; functionally associated CC with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid- CC beta peptide; the interaction is extremely stable in vitro but its CC physiological significance is unclear. May interact with MAPT. May CC interact with MAP2. In the cerebrospinal fluid, interacts with secreted CC SORL1. Interacts with PMEL; this allows the loading of PMEL luminal CC fragment on ILVs to induce fibril nucleation. CC {ECO:0000250|UniProtKB:P02649}. CC -!- INTERACTION: CC P08226; Q9QZM3: Clcf1; NbExp=2; IntAct=EBI-1634131, EBI-3454258; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}. CC Secreted, extracellular space {ECO:0000250|UniProtKB:P02649}. Secreted, CC extracellular space, extracellular matrix CC {ECO:0000250|UniProtKB:P02649}. Extracellular vesicle CC {ECO:0000250|UniProtKB:P02649}. Endosome, multivesicular body CC {ECO:0000250|UniProtKB:P02649}. Note=In the plasma, APOE is associated CC with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL CC lipoproteins. Lipid poor oligomeric APOE is associated with the CC extracellular matrix in a calcium- and heparan-sulfate proteoglycans- CC dependent manner. Lipidation induces the release from the extracellular CC matrix. Colocalizes with CD63 and PMEL at exosomes and in intraluminal CC vesicles within multivesicular endosomes. CC {ECO:0000250|UniProtKB:P02649}. CC -!- PTM: APOE exists as multiple glycosylated and sialylated glycoforms CC within cells and in plasma. The extent of glycosylation and sialylation CC are tissue and context specific. {ECO:0000269|PubMed:29516132}. CC -!- PTM: Glycated in plasma VLDL. {ECO:0000250|UniProtKB:P02649}. CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium. CC {ECO:0000250|UniProtKB:P02649}. CC -!- DISRUPTION PHENOTYPE: APOE knockout mice display severe CC hypercholesterolemia associated with impaired clearance of dietary fats CC (PubMed:1423598). Excess cholesterol is more particularly associated CC with the atherogenic very low and intermediate density lipoproteins in CC the plasma (PubMed:1423598). These mice are therefore prone to CC atherosclerosis (PubMed:1423598). Mice lacking both Cx3cr1 and Apoe CC show decreased atherogenesis (PubMed:12569158). Animals with a double CC knockout of APOE and CD36, fed a Western diet for 12 weeks, exhibit CC much lower levels of CXCL1, CXCL2 and CCL5 mRNA expression in the CC descending aorta and a corresponding decrease in atherosclerotic lesion CC formation, compared to APOE single knockout mice (PubMed:23812099). CC Animals with a double knockout of APOE and TLR4 or TLR6 also have less CC aortic plaque formation than single knockout mice. All 3 double CC knockout show lower serum concentrations of IL1A, ILB and IL18 CC (PubMed:20037584). The melanosomes of APOE knockout mice lack the CC ellipsoidal shape indicative of deficient PMEL amyloidogenesis. CC {ECO:0000269|PubMed:12569158, ECO:0000269|PubMed:1423598, CC ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:23812099, CC ECO:0000269|PubMed:26387950}. CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family. CC {ECO:0000305}. 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; D00466; BAA00361.1; -; Genomic_DNA. DR EMBL; M12414; AAA37251.1; -; mRNA. DR EMBL; BC083351; AAH83351.1; -; mRNA. DR EMBL; M73490; AAA37252.1; -; mRNA. DR CCDS; CCDS20912.1; -. DR PIR; JU0036; JU0036. DR RefSeq; NP_001292748.1; NM_001305819.1. DR RefSeq; NP_001292772.1; NM_001305843.1. DR RefSeq; NP_001292773.1; NM_001305844.1. DR RefSeq; NP_033826.2; NM_009696.4. DR PDB; 1YA9; X-ray; 2.09 A; A=20-200. DR PDBsum; 1YA9; -. DR AlphaFoldDB; P08226; -. DR SMR; P08226; -. DR BioGRID; 198164; 28. DR IntAct; P08226; 6. DR MINT; P08226; -. DR STRING; 10090.ENSMUSP00000133302; -. DR GlyGen; P08226; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P08226; -. DR PhosphoSitePlus; P08226; -. DR CPTAC; non-CPTAC-3396; -. DR CPTAC; non-CPTAC-5578; -. DR jPOST; P08226; -. DR PaxDb; 10090-ENSMUSP00000133302; -. DR PeptideAtlas; P08226; -. DR ProteomicsDB; 283162; -. DR Antibodypedia; 3639; 1615 antibodies from 50 providers. DR DNASU; 11816; -. DR Ensembl; ENSMUST00000003066.16; ENSMUSP00000003066.10; ENSMUSG00000002985.17. DR Ensembl; ENSMUST00000173739.8; ENSMUSP00000133371.2; ENSMUSG00000002985.17. DR Ensembl; ENSMUST00000174064.9; ENSMUSP00000133302.2; ENSMUSG00000002985.17. DR Ensembl; ENSMUST00000174355.8; ENSMUSP00000134160.2; ENSMUSG00000002985.17. DR GeneID; 11816; -. DR KEGG; mmu:11816; -. DR UCSC; uc009fmy.3; mouse. DR AGR; MGI:88057; -. DR CTD; 348; -. DR MGI; MGI:88057; Apoe. DR VEuPathDB; HostDB:ENSMUSG00000002985; -. DR eggNOG; ENOG502QVD6; Eukaryota. DR GeneTree; ENSGT00950000182929; -. DR HOGENOM; CLU_066029_0_0_1; -. DR InParanoid; P08226; -. DR OMA; GHMTDAR; -. DR OrthoDB; 4591103at2759; -. DR PhylomeDB; P08226; -. DR TreeFam; TF334458; -. DR Reactome; R-MMU-3000480; Scavenging by Class A Receptors. DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation. DR Reactome; R-MMU-8963888; Chylomicron assembly. DR Reactome; R-MMU-8963901; Chylomicron remodeling. DR Reactome; R-MMU-8964026; Chylomicron clearance. DR Reactome; R-MMU-8964058; HDL remodeling. DR Reactome; R-MMU-975634; Retinoid metabolism and transport. DR BioGRID-ORCS; 11816; 4 hits in 66 CRISPR screens. DR ChiTaRS; Apoe; mouse. DR EvolutionaryTrace; P08226; -. DR PRO; PR:P08226; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; P08226; Protein. DR Bgee; ENSMUSG00000002985; Expressed in entorhinal cortex and 260 other cell types or tissues. DR ExpressionAtlas; P08226; baseline and differential. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0042627; C:chylomicron; ISO:MGI. DR GO; GO:0034360; C:chylomicron remnant; ISO:MGI. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0034365; C:discoidal high-density lipoprotein particle; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0005768; C:endosome; ISO:MGI. DR GO; GO:0070062; C:extracellular exosome; ISO:MGI. DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; ISO:MGI. DR GO; GO:0005615; C:extracellular space; IDA:ARUK-UCL. DR GO; GO:0031232; C:extrinsic component of external side of plasma membrane; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI. DR GO; GO:0034364; C:high-density lipoprotein particle; ISS:UniProtKB. DR GO; GO:0034363; C:intermediate-density lipoprotein particle; ISS:UniProtKB. DR GO; GO:0005770; C:late endosome; ISO:MGI. DR GO; GO:1990777; C:lipoprotein particle; ISO:MGI. DR GO; GO:0034362; C:low-density lipoprotein particle; IDA:BHF-UCL. DR GO; GO:0042470; C:melanosome; ISO:MGI. DR GO; GO:0097487; C:multivesicular body, internal vesicle; ISO:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; ISO:MGI. DR GO; GO:0043083; C:synaptic cleft; ISO:MGI. DR GO; GO:0034361; C:very-low-density lipoprotein particle; ISS:UniProtKB. DR GO; GO:0001540; F:amyloid-beta binding; ISS:UniProtKB. DR GO; GO:0016209; F:antioxidant activity; ISO:MGI. DR GO; GO:0120020; F:cholesterol transfer activity; IDA:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB. DR GO; GO:0046848; F:hydroxyapatite binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB. DR GO; GO:0008289; F:lipid binding; ISO:MGI. DR GO; GO:0005319; F:lipid transporter activity; ISO:MGI. DR GO; GO:0071813; F:lipoprotein particle binding; IDA:MGI. DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISS:UniProtKB. DR GO; GO:0046911; F:metal chelating activity; ISO:MGI. DR GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; IMP:BHF-UCL. DR GO; GO:0005543; F:phospholipid binding; ISO:MGI. DR GO; GO:0046983; F:protein dimerization activity; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI. DR GO; GO:0048156; F:tau protein binding; ISO:MGI. DR GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; ISO:MGI. DR GO; GO:0097113; P:AMPA glutamate receptor clustering; ISO:MGI. DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISO:MGI. DR GO; GO:0048844; P:artery morphogenesis; IGI:MGI. DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI. DR GO; GO:0006707; P:cholesterol catabolic process; IMP:MGI. DR GO; GO:0033344; P:cholesterol efflux; IDA:MGI. DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL. DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI. DR GO; GO:0034382; P:chylomicron remnant clearance; ISS:UniProtKB. DR GO; GO:0072359; P:circulatory system development; IMP:MGI. DR GO; GO:0055089; P:fatty acid homeostasis; ISO:MGI. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI. DR GO; GO:0010467; P:gene expression; IGI:MGI. DR GO; GO:0034380; P:high-density lipoprotein particle assembly; ISS:UniProtKB. DR GO; GO:0034384; P:high-density lipoprotein particle clearance; ISO:MGI. DR GO; GO:0034375; P:high-density lipoprotein particle remodeling; ISO:MGI. DR GO; GO:0071831; P:intermediate-density lipoprotein particle clearance; ISS:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:MGI. DR GO; GO:0055088; P:lipid homeostasis; IMP:MGI. DR GO; GO:0006629; P:lipid metabolic process; IGI:MGI. DR GO; GO:0006869; P:lipid transport; ISO:MGI. DR GO; GO:0010877; P:lipid transport involved in lipid storage; IMP:BHF-UCL. DR GO; GO:0042158; P:lipoprotein biosynthetic process; IGI:MGI. DR GO; GO:0042159; P:lipoprotein catabolic process; IMP:MGI. DR GO; GO:0042157; P:lipoprotein metabolic process; IMP:MGI. DR GO; GO:0035641; P:locomotory exploration behavior; ISO:MGI. DR GO; GO:0015909; P:long-chain fatty acid transport; ISO:MGI. DR GO; GO:0007616; P:long-term memory; ISO:MGI. DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; IMP:BHF-UCL. DR GO; GO:0051651; P:maintenance of location in cell; IMP:MGI. DR GO; GO:0032438; P:melanosome organization; IMP:UniProtKB. DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; IMP:UniProtKB. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:MGI. DR GO; GO:0030195; P:negative regulation of blood coagulation; ISO:MGI. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:MGI. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI. DR GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; ISO:MGI. DR GO; GO:0090370; P:negative regulation of cholesterol efflux; ISO:MGI. DR GO; GO:0061000; P:negative regulation of dendritic spine development; ISO:MGI. DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; ISO:MGI. DR GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:MGI. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISO:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; IGI:UniProtKB. DR GO; GO:0051055; P:negative regulation of lipid biosynthetic process; ISO:MGI. DR GO; GO:1903001; P:negative regulation of lipid transport across blood-brain barrier; ISO:MGI. DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISO:MGI. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI. DR GO; GO:1902999; P:negative regulation of phospholipid efflux; ISO:MGI. DR GO; GO:0010544; P:negative regulation of platelet activation; ISO:MGI. DR GO; GO:1901627; P:negative regulation of postsynaptic membrane organization; ISO:MGI. DR GO; GO:0051248; P:negative regulation of protein metabolic process; ISO:MGI. DR GO; GO:0050709; P:negative regulation of protein secretion; ISO:MGI. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IGI:BHF-UCL. DR GO; GO:0090209; P:negative regulation of triglyceride metabolic process; IGI:MGI. DR GO; GO:0031175; P:neuron projection development; ISO:MGI. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:MGI. DR GO; GO:0097114; P:NMDA glutamate receptor clustering; ISO:MGI. DR GO; GO:0033700; P:phospholipid efflux; ISO:MGI. DR GO; GO:0044794; P:positive regulation by host of viral process; ISO:MGI. DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; IMP:UniProtKB. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISO:MGI. DR GO; GO:0045773; P:positive regulation of axon extension; ISO:MGI. DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:ARUK-UCL. DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IMP:BHF-UCL. DR GO; GO:1905920; P:positive regulation of CoA-transferase activity; IMP:BHF-UCL. DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI. DR GO; GO:1902952; P:positive regulation of dendritic spine maintenance; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISO:MGI. DR GO; GO:1903002; P:positive regulation of lipid transport across blood-brain barrier; ISO:MGI. DR GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; ISO:MGI. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:MGI. DR GO; GO:1902998; P:positive regulation of neurofibrillary tangle assembly; ISO:MGI. DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:ARUK-UCL. DR GO; GO:1902995; P:positive regulation of phospholipid efflux; ISO:MGI. DR GO; GO:1901631; P:positive regulation of presynaptic membrane organization; ISO:MGI. DR GO; GO:0017038; P:protein import; ISO:MGI. DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:MGI. DR GO; GO:1905906; P:regulation of amyloid fibril formation; ISO:MGI. DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; ISO:MGI. DR GO; GO:1900221; P:regulation of amyloid-beta clearance; ISO:MGI. DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:2000822; P:regulation of behavioral fear response; ISO:MGI. DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; ISO:MGI. DR GO; GO:1905890; P:regulation of cellular response to very-low-density lipoprotein particle stimulus; ISO:MGI. DR GO; GO:0090181; P:regulation of cholesterol metabolic process; ISO:MGI. DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI. DR GO; GO:0045088; P:regulation of innate immune response; IMP:UniProtKB. DR GO; GO:0097006; P:regulation of plasma lipoprotein particle levels; IMP:BHF-UCL. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; ISO:MGI. DR GO; GO:0051246; P:regulation of protein metabolic process; ISO:MGI. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISO:MGI. DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO. DR GO; GO:0090207; P:regulation of triglyceride metabolic process; ISO:MGI. DR GO; GO:0061771; P:response to caloric restriction; ISO:MGI. DR GO; GO:0002021; P:response to dietary excess; IMP:MGI. DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI. DR GO; GO:0043691; P:reverse cholesterol transport; ISO:MGI. DR GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB. DR GO; GO:0006641; P:triglyceride metabolic process; ISO:MGI. DR GO; GO:0071830; P:triglyceride-rich lipoprotein particle clearance; IMP:UniProtKB. DR GO; GO:0042311; P:vasodilation; IMP:MGI. DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; ISS:UniProtKB. DR GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; IMP:BHF-UCL. DR GO; GO:0019068; P:virion assembly; ISO:MGI. DR Gene3D; 1.20.120.20; Apolipoprotein; 2. DR InterPro; IPR000074; ApoA_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. DR Genevisible; P08226; MM. PE 1: Evidence at protein level; KW 3D-structure; Chylomicron; Direct protein sequencing; Endosome; KW Extracellular matrix; Glycoprotein; HDL; Heparin-binding; Lipid transport; KW Lipid-binding; Oxidation; Phosphoprotein; Reference proteome; Repeat; KW Secreted; Signal; Transport; VLDL. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..311 FT /note="Apolipoprotein E" FT /id="PRO_0000001990" FT REPEAT 72..93 FT /note="1" FT REPEAT 94..115 FT /note="2" FT REPEAT 116..137 FT /note="3" FT REPEAT 138..159 FT /note="4" FT REPEAT 160..181 FT /note="5" FT REPEAT 182..203 FT /note="6" FT REPEAT 204..225 FT /note="7" FT REPEAT 226..247 FT /note="8" FT REGION 72..247 FT /note="8 X 22 AA approximate tandem repeats" FT REGION 150..160 FT /note="LDL and other lipoprotein receptors binding" FT /evidence="ECO:0000250|UniProtKB:P02649" FT REGION 202..282 FT /note="Lipid-binding and lipoprotein association" FT /evidence="ECO:0000250|UniProtKB:P02649" FT REGION 258..311 FT /note="Homooligomerization" FT /evidence="ECO:0000250|UniProtKB:P02649" FT REGION 270..282 FT /note="Specificity for association with VLDL" FT /evidence="ECO:0000250|UniProtKB:P02649" FT BINDING 154..157 FT /ligand="heparin" FT /ligand_id="ChEBI:CHEBI:28304" FT /evidence="ECO:0000250|UniProtKB:P02649" FT BINDING 221..228 FT /ligand="heparin" FT /ligand_id="ChEBI:CHEBI:28304" FT /evidence="ECO:0000250|UniProtKB:P02649" FT MOD_RES 135 FT /note="Methionine sulfoxide" FT /evidence="ECO:0000269|PubMed:16876491" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CONFLICT 163 FT /note="E -> D (in Ref. 2; AAA37251)" FT /evidence="ECO:0000305" FT HELIX 29..31 FT /evidence="ECO:0007829|PDB:1YA9" FT HELIX 34..50 FT /evidence="ECO:0007829|PDB:1YA9" FT HELIX 55..62 FT /evidence="ECO:0007829|PDB:1YA9" FT HELIX 65..90 FT /evidence="ECO:0007829|PDB:1YA9" FT HELIX 97..134 FT /evidence="ECO:0007829|PDB:1YA9" FT TURN 135..137 FT /evidence="ECO:0007829|PDB:1YA9" FT HELIX 141..172 FT /evidence="ECO:0007829|PDB:1YA9" FT HELIX 184..191 FT /evidence="ECO:0007829|PDB:1YA9" SQ SEQUENCE 311 AA; 35867 MW; 3B36FA897CC34170 CRC64; MKALWAVLLV TLLTGCLAEG EPEVTDQLEW QSNQPWEQAL NRFWDYLRWV QTLSDQVQEE LQSSQVTQEL TALMEDTMTE VKAYKKELEE QLGPVAEETR ARLGKEVQAA QARLGADMED LRNRLGQYRN EVHTMLGQST EEIRARLSTH LRKMRKRLMR DAEDLQKRLA VYKAGAREGA ERGVSAIRER LGPLVEQGRQ RTANLGAGAA QPLRDRAQAF GDRIRGRLEE VGNQARDRLE EVREHMEEVR SKMEEQTQQI RLQAEIFQAR LKGWFEPIVE DMHRQWANLM EKIQASVATN PIITPVAQEN Q //