APOE_MOUSE
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 03-AUG-2022, entry version 204.
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, Pancreas,
RC 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/jci200315555;
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 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. Apoliproteins 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 (By similarity). May interact with ABCA1;
CC functionally associated with ABCA1 in the biogenesis of HDLs (By
CC similarity). May interact with APP/A4 amyloid-beta peptide; the
CC interaction is extremely stable in vitro but its physiological
CC significance is unclear (By similarity). May interact with MAPT (By
CC similarity). May interact with MAP2. In the cerebrospinal fluid,
CC interacts with secreted SORL1 (By similarity).
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}. 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. {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). {ECO:0000269|PubMed:12569158,
CC ECO:0000269|PubMed:1423598, ECO:0000269|PubMed:20037584,
CC ECO:0000269|PubMed:23812099}.
CC -!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
CC {ECO:0000305}.
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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 iPTMnet; P08226; -.
DR PhosphoSitePlus; P08226; -.
DR CPTAC; non-CPTAC-3396; -.
DR CPTAC; non-CPTAC-5578; -.
DR jPOST; P08226; -.
DR PaxDb; P08226; -.
DR PeptideAtlas; P08226; -.
DR PRIDE; P08226; -.
DR ProteomicsDB; 283162; -.
DR Antibodypedia; 3639; 1433 antibodies from 50 providers.
DR DNASU; 11816; -.
DR Ensembl; ENSMUST00000003066; ENSMUSP00000003066; ENSMUSG00000002985.
DR Ensembl; ENSMUST00000173739; ENSMUSP00000133371; ENSMUSG00000002985.
DR Ensembl; ENSMUST00000174064; ENSMUSP00000133302; ENSMUSG00000002985.
DR Ensembl; ENSMUST00000174355; ENSMUSP00000134160; ENSMUSG00000002985.
DR GeneID; 11816; -.
DR KEGG; mmu:11816; -.
DR UCSC; uc009fmy.3; mouse.
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; WFEPLVQ; -.
DR OrthoDB; 1314660at2759; -.
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 63 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 256 other tissues.
DR ExpressionAtlas; P08226; baseline and differential.
DR Genevisible; P08226; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0042627; C:chylomicron; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; 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:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005768; C:endosome; 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:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; 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:0007568; P:aging; 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:0006874; P:cellular calcium ion homeostasis; IDA: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: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: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:0043407; P:negative regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; 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: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:1905855; P:positive regulation of heparan sulfate binding; ISO:MGI.
DR GO; GO:1905860; P:positive regulation of heparan sulfate proteoglycan binding; 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:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:ARUK-UCL.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
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:0045893; P:positive regulation of transcription, DNA-templated; 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:1901214; P:regulation of neuron death; ISO:MGI.
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:1902947; P:regulation of tau-protein kinase activity; ISO:MGI.
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 InterPro; IPR000074; ApoA_E.
DR Pfam; PF01442; Apolipoprotein; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chylomicron; Direct protein sequencing; Extracellular matrix;
KW Glycoprotein; HDL; Heparin-binding; Lipid transport; Lipid-binding;
KW Oxidation; Phosphoprotein; Reference proteome; Repeat; Secreted; Signal;
KW 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
