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Apolipoprotein E (Apo-E)

 APOE_RAT                Reviewed;         312 AA.
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 2.
22-NOV-2017, entry version 153.
RecName: Full=Apolipoprotein E;
Flags: Precursor;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
PubMed=3797247; DOI=10.1093/nar/14.23.9527;
Fukazawa C., Matsumoto A., Taylor L.M.;
"Complete nucleotide sequence of the gene encoding the rat
apolipoprotein E.";
Nucleic Acids Res. 14:9527-9528(1986).
Fung W.-P., Howlett G.J., Schreiber G.;
"Structure and expression of the rat apolipoprotein E gene.";
J. Biol. Chem. 261:13777-13783(1986).
McLean J.W., Fukazawa C., Taylor J.M.;
"Rat apolipoprotein E mRNA. Cloning and sequencing of double-stranded
J. Biol. Chem. 258:8993-9000(1983).
PubMed=7766086; DOI=10.1007/BF00191183;
Nomura N., Yamada H., Matsubara N., Horinouchi S., Beppu T.;
"Secretion by Saccharomyces cerevisiae of rat apolipoprotein E as a
fusion to Mucor rennin.";
Appl. Microbiol. Biotechnol. 42:865-870(1995).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
PROTEIN SEQUENCE OF 87-100; 114-122; 130-144; 191-199; 202-216;
STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
Lubec G., Chen W.-Q.;
Submitted (APR-2007) to UniProtKB.
PubMed=22673903; DOI=10.1038/ncomms1871;
Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
Lundby C., Olsen J.V.;
"Quantitative maps of protein phosphorylation sites across 14
different rat organs and tissues.";
Nat. Commun. 3:876-876(2012).
-!- FUNCTION: Mediates the binding, internalization, and catabolism of
lipoprotein particles. It can serve as a ligand for the LDL (apo
B/E) receptor and for the specific apo-E receptor (chylomicron
remnant) of hepatic tissues. {ECO:0000250|UniProtKB:P02649}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}.
-!- TISSUE SPECIFICITY: Secreted in plasma.
-!- PTM: Phosphorylated by FAM20C in the extracellular medium.
-!- MISCELLANEOUS: The mature protein has no cysteine residues;
however, in different allelic variants where cysteine residues
replace arginine at positions 155 or 168, binding of Apo-E to cell
membrane receptors is decreased. The amino end of this protein is
therefore thought to interact with the receptor.
-!- SIMILARITY: Belongs to the apolipoprotein A1/A4/E family.
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
EMBL; X04979; CAA28650.1; -; Genomic_DNA.
EMBL; J02582; AAA40755.1; -; Genomic_DNA.
EMBL; S76779; AAC60703.1; -; mRNA.
EMBL; BC086581; AAH86581.1; -; mRNA.
PIR; A26189; LPRTE.
RefSeq; NP_001257610.1; NM_001270681.1.
RefSeq; NP_001257611.1; NM_001270682.1.
RefSeq; NP_001257612.1; NM_001270683.1.
RefSeq; NP_001257613.1; NM_001270684.1.
RefSeq; NP_620183.2; NM_138828.3.
UniGene; Rn.32351; -.
ProteinModelPortal; P02650; -.
SMR; P02650; -.
BioGrid; 247757; 2.
IntAct; P02650; 3.
MINT; MINT-4585732; -.
STRING; 10116.ENSRNOP00000050968; -.
iPTMnet; P02650; -.
PhosphoSitePlus; P02650; -.
PaxDb; P02650; -.
PRIDE; P02650; -.
Ensembl; ENSRNOT00000041891; ENSRNOP00000050968; ENSRNOG00000018454.
Ensembl; ENSRNOT00000091574; ENSRNOP00000068937; ENSRNOG00000018454.
GeneID; 25728; -.
KEGG; rno:25728; -.
UCSC; RGD:2138; rat.
CTD; 348; -.
RGD; 2138; Apoe.
eggNOG; ENOG410IVK0; Eukaryota.
GeneTree; ENSGT00730000111315; -.
HOGENOM; HOG000034006; -.
HOVERGEN; HBG010582; -.
InParanoid; P02650; -.
KO; K04524; -.
PhylomeDB; P02650; -.
TreeFam; TF334458; -.
Reactome; R-RNO-3000480; Scavenging by Class A Receptors.
Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
Reactome; R-RNO-8963888; Chylomicron assembly.
Reactome; R-RNO-8963901; Chylomicron remodeling.
Reactome; R-RNO-8964026; Chylomicron clearance.
Reactome; R-RNO-8964058; HDL remodeling.
Reactome; R-RNO-975634; Retinoid metabolism and transport.
PRO; PR:P02650; -.
Proteomes; UP000002494; Chromosome 1.
Bgee; ENSRNOG00000018454; -.
ExpressionAtlas; P02650; baseline and differential.
Genevisible; P02650; RN.
GO; GO:0072562; C:blood microparticle; ISO:RGD.
GO; GO:0009986; C:cell surface; IDA:RGD.
GO; GO:0042627; C:chylomicron; IDA:RGD.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0030425; C:dendrite; IDA:RGD.
GO; GO:0034365; C:discoidal high-density lipoprotein particle; IDA:RGD.
GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
GO; GO:0005768; C:endosome; IDA:RGD.
GO; GO:0070062; C:extracellular exosome; ISO:RGD.
GO; GO:0031012; C:extracellular matrix; ISO:RGD.
GO; GO:0005576; C:extracellular region; ISO:RGD.
GO; GO:0005615; C:extracellular space; IDA:RGD.
GO; GO:1903561; C:extracellular vesicle; ISO:RGD.
GO; GO:0031232; C:extrinsic component of external side of plasma membrane; IDA:RGD.
GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
GO; GO:0034364; C:high-density lipoprotein particle; IDA:ARUK-UCL.
GO; GO:0034363; C:intermediate-density lipoprotein particle; IDA:ARUK-UCL.
GO; GO:0005770; C:late endosome; IDA:RGD.
GO; GO:1990777; C:lipoprotein particle; ISO:RGD.
GO; GO:0034362; C:low-density lipoprotein particle; IDA:ARUK-UCL.
GO; GO:0005764; C:lysosome; IDA:RGD.
GO; GO:0016020; C:membrane; ISO:RGD.
GO; GO:0043025; C:neuronal cell body; IDA:RGD.
GO; GO:0005635; C:nuclear envelope; IDA:RGD.
GO; GO:0005634; C:nucleus; ISO:RGD.
GO; GO:0005886; C:plasma membrane; IDA:RGD.
GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:ARUK-UCL.
GO; GO:0001540; F:amyloid-beta binding; IDA:RGD.
GO; GO:0016209; F:antioxidant activity; ISO:RGD.
GO; GO:0015485; F:cholesterol binding; IBA:GO_Central.
GO; GO:0017127; F:cholesterol transporter activity; ISO:RGD.
GO; GO:0008201; F:heparin binding; ISO:RGD.
GO; GO:0046848; F:hydroxyapatite binding; IDA:RGD.
GO; GO:0042802; F:identical protein binding; ISO:RGD.
GO; GO:0008289; F:lipid binding; ISO:RGD.
GO; GO:0005319; F:lipid transporter activity; IDA:RGD.
GO; GO:0071813; F:lipoprotein particle binding; ISO:RGD.
GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:RGD.
GO; GO:0046911; F:metal chelating activity; ISO:RGD.
GO; GO:0060228; F:phosphatidylcholine-sterol O-acyltransferase activator activity; ISO:RGD.
GO; GO:0005543; F:phospholipid binding; IDA:RGD.
GO; GO:0046983; F:protein dimerization activity; ISO:RGD.
GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
GO; GO:0005102; F:receptor binding; IPI:UniProtKB.
GO; GO:0048156; F:tau protein binding; ISO:RGD.
GO; GO:0070326; F:very-low-density lipoprotein particle receptor binding; ISO:RGD.
GO; GO:0007568; P:aging; IDA:RGD.
GO; GO:0097113; P:AMPA glutamate receptor clustering; ISO:RGD.
GO; GO:0042982; P:amyloid precursor protein metabolic process; ISO:RGD.
GO; GO:0048844; P:artery morphogenesis; ISO:RGD.
GO; GO:0072358; P:cardiovascular system development; ISO:RGD.
GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
GO; GO:0071397; P:cellular response to cholesterol; IEP:RGD.
GO; GO:0071361; P:cellular response to ethanol; IEP:RGD.
GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
GO; GO:0019934; P:cGMP-mediated signaling; ISO:RGD.
GO; GO:0006707; P:cholesterol catabolic process; ISO:RGD.
GO; GO:0033344; P:cholesterol efflux; ISO:RGD.
GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
GO; GO:0034382; P:chylomicron remnant clearance; ISO:RGD.
GO; GO:0055089; P:fatty acid homeostasis; ISO:RGD.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; ISO:RGD.
GO; GO:0034380; P:high-density lipoprotein particle assembly; ISO:RGD.
GO; GO:0034384; P:high-density lipoprotein particle clearance; ISO:RGD.
GO; GO:0034375; P:high-density lipoprotein particle remodeling; ISO:RGD.
GO; GO:0055088; P:lipid homeostasis; ISO:RGD.
GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
GO; GO:0006869; P:lipid transport; IDA:RGD.
GO; GO:0010877; P:lipid transport involved in lipid storage; ISO:RGD.
GO; GO:0042158; P:lipoprotein biosynthetic process; ISO:RGD.
GO; GO:0042159; P:lipoprotein catabolic process; ISO:RGD.
GO; GO:0042157; P:lipoprotein metabolic process; IDA:RGD.
GO; GO:0035641; P:locomotory exploration behavior; ISO:RGD.
GO; GO:0015909; P:long-chain fatty acid transport; ISO:RGD.
GO; GO:0007616; P:long-term memory; ISO:RGD.
GO; GO:0034374; P:low-density lipoprotein particle remodeling; ISO:RGD.
GO; GO:0051651; P:maintenance of location in cell; ISO:RGD.
GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:RGD.
GO; GO:0030195; P:negative regulation of blood coagulation; ISO:RGD.
GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:RGD.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
GO; GO:0032269; P:negative regulation of cellular protein metabolic process; ISO:RGD.
GO; GO:0045541; P:negative regulation of cholesterol biosynthetic process; IDA:RGD.
GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISO:RGD.
GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISO:RGD.
GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:RGD.
GO; GO:1901215; P:negative regulation of neuron death; ISO:RGD.
GO; GO:0010977; P:negative regulation of neuron projection development; ISO:RGD.
GO; GO:0010544; P:negative regulation of platelet activation; ISO:RGD.
GO; GO:1901630; P:negative regulation of presynaptic membrane organization; ISO:RGD.
GO; GO:0090209; P:negative regulation of triglyceride metabolic process; ISO:RGD.
GO; GO:0031102; P:neuron projection regeneration; TAS:RGD.
GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:RGD.
GO; GO:0097114; P:NMDA glutamate receptor clustering; ISO:RGD.
GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
GO; GO:0014012; P:peripheral nervous system axon regeneration; IEP:RGD.
GO; GO:0033700; P:phospholipid efflux; ISO:RGD.
GO; GO:0044794; P:positive regulation by host of viral process; ISO:RGD.
GO; GO:0045773; P:positive regulation of axon extension; IDA:RGD.
GO; GO:0030828; P:positive regulation of cGMP biosynthetic process; ISO:RGD.
GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:RGD.
GO; GO:0010873; P:positive regulation of cholesterol esterification; ISO:RGD.
GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:RGD.
GO; GO:1902952; P:positive regulation of dendritic spine maintenance; ISO:RGD.
GO; GO:0045807; P:positive regulation of endocytosis; ISO:RGD.
GO; GO:1905855; P:positive regulation of heparan sulfate binding; ISO:RGD.
GO; GO:1905860; P:positive regulation of heparan sulfate proteoglycan binding; ISO:RGD.
GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISO:RGD.
GO; GO:1903002; P:positive regulation of lipid transport across blood brain barrier; ISO:RGD.
GO; GO:0032805; P:positive regulation of low-density lipoprotein particle receptor catabolic process; ISO:RGD.
GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:RGD.
GO; GO:0010976; P:positive regulation of neuron projection development; ISO:RGD.
GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:RGD.
GO; GO:1902995; P:positive regulation of phospholipid efflux; ISO:RGD.
GO; GO:1901628; P:positive regulation of postsynaptic membrane organization; ISO:RGD.
GO; GO:0017038; P:protein import; ISO:RGD.
GO; GO:0006898; P:receptor-mediated endocytosis; ISO:RGD.
GO; GO:1905906; P:regulation of amyloid fibril formation; ISO:RGD.
GO; GO:1900221; P:regulation of amyloid-beta clearance; ISO:RGD.
GO; GO:2000822; P:regulation of behavioral fear response; ISO:RGD.
GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; ISO:RGD.
GO; GO:1905890; P:regulation of cellular response to very-low-density lipoprotein particle stimulus; ISO:RGD.
GO; GO:0090181; P:regulation of cholesterol metabolic process; ISO:RGD.
GO; GO:0032374; P:regulation of cholesterol transport; IBA:GO_Central.
GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
GO; GO:0097006; P:regulation of plasma lipoprotein particle levels; ISO:RGD.
GO; GO:0032462; P:regulation of protein homooligomerization; ISO:RGD.
GO; GO:0051246; P:regulation of protein metabolic process; ISO:RGD.
GO; GO:0090207; P:regulation of triglyceride metabolic process; IDA:RGD.
GO; GO:0061771; P:response to caloric restriction; ISO:RGD.
GO; GO:1904421; P:response to D-galactosamine; IEP:RGD.
GO; GO:0002021; P:response to dietary excess; ISO:RGD.
GO; GO:0045471; P:response to ethanol; IEP:RGD.
GO; GO:0032868; P:response to insulin; IEP:RGD.
GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
GO; GO:0034612; P:response to tumor necrosis factor; IEP:RGD.
GO; GO:0010043; P:response to zinc ion; IEP:RGD.
GO; GO:0043691; P:reverse cholesterol transport; ISO:RGD.
GO; GO:0019433; P:triglyceride catabolic process; IBA:GO_Central.
GO; GO:0070328; P:triglyceride homeostasis; ISO:RGD.
GO; GO:0006641; P:triglyceride metabolic process; ISO:RGD.
GO; GO:0042311; P:vasodilation; ISO:RGD.
GO; GO:0034447; P:very-low-density lipoprotein particle clearance; ISO:RGD.
GO; GO:0034372; P:very-low-density lipoprotein particle remodeling; ISO:RGD.
GO; GO:0019068; P:virion assembly; ISO:RGD.
InterPro; IPR000074; ApoA_E.
Pfam; PF01442; Apolipoprotein; 1.
1: Evidence at protein level;
Chylomicron; Complete proteome; Direct protein sequencing;
Glycoprotein; HDL; Heparin-binding; Lipid transport; Oxidation;
Phosphoprotein; Reference proteome; Repeat; Secreted; Signal;
Transport; VLDL.
CHAIN 19 312 Apolipoprotein E.
REPEAT 72 93 1.
REPEAT 94 115 2.
REPEAT 116 137 3.
REPEAT 138 159 4.
REPEAT 160 181 5.
REPEAT 182 203 6.
REPEAT 204 225 7.
REPEAT 226 247 8.
REGION 72 247 8 X 22 AA approximate tandem repeats.
REGION 150 160 LDL receptor binding.
REGION 154 157 Heparin-binding.
REGION 221 228 Heparin-binding.
MOD_RES 135 135 Methionine sulfoxide.
MOD_RES 139 139 Phosphoserine.
CARBOHYD 25 25 O-linked (GalNAc...) threonine.
CARBOHYD 305 305 O-linked (GalNAc...) threonine.
CONFLICT 104 104 A -> T (in Ref. 1; CAA28650).
CONFLICT 110 110 A -> T (in Ref. 3; no nucleotide entry
and 4; AAC60703). {ECO:0000305}.
CONFLICT 141 141 E -> D (in Ref. 3; no nucleotide entry
and 4; AAC60703). {ECO:0000305}.
CONFLICT 206 213 GAGAAQPL -> RWRRPAP (in Ref. 1; CAA28650
and 3; no nucleotide entry).
CONFLICT 309 310 LE -> WR (in Ref. 3; no nucleotide entry
and 4; AAC60703). {ECO:0000305}.
SEQUENCE 312 AA; 35753 MW; 8180EEE933378D92 CRC64;

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