UniProtKB - Q7M2U8 (APOE_SHEEP)
Protein
Apolipoprotein E
Gene
APOE
Organism
Ovis aries (Sheep)
Status
Functioni
APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells.By similarity
GO - Molecular functioni
- amyloid-beta binding Source: Ensembl
- antioxidant activity Source: Ensembl
- cholesterol transfer activity Source: Ensembl
- heparan sulfate proteoglycan binding Source: UniProtKB
- heparin binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- lipoprotein particle binding Source: Ensembl
- low-density lipoprotein particle receptor binding Source: UniProtKB
- metal chelating activity Source: Ensembl
- phosphatidylcholine-sterol O-acyltransferase activator activity Source: Ensembl
- phospholipid binding Source: Ensembl
- protein homodimerization activity Source: Ensembl
- tau protein binding Source: Ensembl
- very-low-density lipoprotein particle receptor binding Source: Ensembl
GO - Biological processi
- AMPA glutamate receptor clustering Source: Ensembl
- amyloid precursor protein metabolic process Source: Ensembl
- artery morphogenesis Source: Ensembl
- cellular calcium ion homeostasis Source: Ensembl
- cGMP-mediated signaling Source: Ensembl
- cholesterol catabolic process Source: Ensembl
- cholesterol efflux Source: UniProtKB
- cholesterol homeostasis Source: Ensembl
- chylomicron remnant clearance Source: UniProtKB
- fatty acid homeostasis Source: Ensembl
- G protein-coupled receptor signaling pathway Source: Ensembl
- high-density lipoprotein particle assembly Source: UniProtKB
- high-density lipoprotein particle clearance Source: Ensembl
- high-density lipoprotein particle remodeling Source: Ensembl
- intermediate-density lipoprotein particle clearance Source: UniProtKB
- lipid transport involved in lipid storage Source: Ensembl
- lipoprotein biosynthetic process Source: UniProtKB
- lipoprotein catabolic process Source: Ensembl
- locomotory exploration behavior Source: Ensembl
- long-chain fatty acid transport Source: Ensembl
- long-term memory Source: Ensembl
- low-density lipoprotein particle remodeling Source: Ensembl
- maintenance of location in cell Source: Ensembl
- negative regulation of amyloid-beta formation Source: Ensembl
- negative regulation of amyloid fibril formation Source: UniProtKB
- negative regulation of blood vessel endothelial cell migration Source: Ensembl
- negative regulation of canonical Wnt signaling pathway Source: Ensembl
- negative regulation of cholesterol biosynthetic process Source: Ensembl
- negative regulation of endothelial cell proliferation Source: Ensembl
- negative regulation of gene expression Source: Ensembl
- negative regulation of inflammatory response Source: Ensembl
- negative regulation of long-term synaptic potentiation Source: Ensembl
- negative regulation of MAP kinase activity Source: Ensembl
- negative regulation of neuron projection development Source: Ensembl
- negative regulation of platelet activation Source: Ensembl
- negative regulation of protein secretion Source: Ensembl
- negative regulation of triglyceride metabolic process Source: Ensembl
- neuron projection development Source: Ensembl
- nitric oxide mediated signal transduction Source: Ensembl
- NMDA glutamate receptor clustering Source: Ensembl
- phospholipid efflux Source: Ensembl
- positive regulation by host of viral process Source: Ensembl
- positive regulation of amyloid-beta clearance Source: UniProtKB
- positive regulation of cholesterol efflux Source: Ensembl
- positive regulation of cholesterol esterification Source: Ensembl
- positive regulation of dendritic spine development Source: Ensembl
- positive regulation of dendritic spine maintenance Source: Ensembl
- positive regulation of endocytosis Source: Ensembl
- positive regulation of ERK1 and ERK2 cascade Source: Ensembl
- positive regulation of heparan sulfate binding Source: Ensembl
- positive regulation of heparan sulfate proteoglycan binding Source: Ensembl
- positive regulation of lipid biosynthetic process Source: Ensembl
- positive regulation of lipid transport across blood-brain barrier Source: Ensembl
- positive regulation of low-density lipoprotein particle receptor catabolic process Source: Ensembl
- positive regulation of membrane protein ectodomain proteolysis Source: Ensembl
- positive regulation of nitric-oxide synthase activity Source: Ensembl
- positive regulation of phospholipid efflux Source: Ensembl
- positive regulation of transcription, DNA-templated Source: Ensembl
- protein import Source: Ensembl
- receptor-mediated endocytosis Source: Ensembl
- regulation of apoptotic process Source: Ensembl
- regulation of behavioral fear response Source: Ensembl
- regulation of Cdc42 protein signal transduction Source: Ensembl
- regulation of cellular response to very-low-density lipoprotein particle stimulus Source: Ensembl
- regulation of innate immune response Source: Ensembl
- regulation of proteasomal protein catabolic process Source: Ensembl
- regulation of protein-containing complex assembly Source: Ensembl
- response to caloric restriction Source: Ensembl
- response to dietary excess Source: Ensembl
- response to oxidative stress Source: Ensembl
- reverse cholesterol transport Source: Ensembl
- triglyceride homeostasis Source: Ensembl
- triglyceride metabolic process Source: Ensembl
- triglyceride-rich lipoprotein particle clearance Source: UniProtKB
- vasodilation Source: Ensembl
- very-low-density lipoprotein particle clearance Source: UniProtKB
- very-low-density lipoprotein particle remodeling Source: Ensembl
- virion assembly Source: Ensembl
Keywordsi
Molecular function | Heparin-binding |
Biological process | Lipid transport, Transport |
Ligand | Lipid-binding |
Names & Taxonomyi
Protein namesi | Recommended name: Apolipoprotein EShort name: Apo-E |
Gene namesi | Name:APOE |
Organismi | Ovis aries (Sheep) |
Taxonomic identifieri | 9940 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Caprinae › Ovis |
Proteomesi |
|
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
- extracellular space By similarity
- extracellular matrix By similarity
Note: In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins. Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner. Lipidation induces the release from the extracellular matrix.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: Ensembl
Extracellular region or secreted
- chylomicron Source: UniProtKB-KW
- extracellular matrix Source: UniProtKB
- extracellular space Source: UniProtKB
- high-density lipoprotein particle Source: UniProtKB
- intermediate-density lipoprotein particle Source: UniProtKB
- low-density lipoprotein particle Source: UniProtKB
- synaptic cleft Source: Ensembl
- very-low-density lipoprotein particle Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: Ensembl
Plasma Membrane
- plasma membrane Source: GOC
Other locations
- glutamatergic synapse Source: Ensembl
Keywords - Cellular componenti
Chylomicron, Extracellular matrix, HDL, Secreted, VLDLPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
ChainiPRO_0000001997 | 19 – 316 | Apolipoprotein EAdd BLAST | 298 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 142 | Methionine sulfoxideBy similarity | 1 | |
Modified residuei | 146 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma. The extent of glycosylation and sialylation are tissue and context specific.By similarity
Glycated in plasma VLDL.By similarity
Phosphorylated by FAM20C in the extracellular medium.By similarity
Keywords - PTMi
Glycoprotein, Oxidation, PhosphoproteinInteractioni
Subunit structurei
Homotetramer. May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear. May interact with MAPT. May interact with MAP2. In the cerebrospinal fluid, interacts with secreted SORL1.
By similarityGO - Molecular functioni
- heparan sulfate proteoglycan binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- low-density lipoprotein particle receptor binding Source: UniProtKB
- protein homodimerization activity Source: Ensembl
- tau protein binding Source: Ensembl
- very-low-density lipoprotein particle receptor binding Source: Ensembl
Protein-protein interaction databases
STRINGi | 9940.ENSOARP00000010129 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 79 – 100 | 1Add BLAST | 22 | |
Repeati | 101 – 122 | 2Add BLAST | 22 | |
Repeati | 123 – 144 | 3Add BLAST | 22 | |
Repeati | 145 – 166 | 4Add BLAST | 22 | |
Repeati | 167 – 188 | 5Add BLAST | 22 | |
Repeati | 189 – 210 | 6Add BLAST | 22 | |
Repeati | 211 – 232 | 7Add BLAST | 22 | |
Repeati | 233 – 254 | 8Add BLAST | 22 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 79 – 254 | 8 X 22 AA approximate tandem repeatsAdd BLAST | 176 | |
Regioni | 157 – 167 | LDL and other lipoprotein receptors bindingBy similarityAdd BLAST | 11 | |
Regioni | 161 – 164 | Heparin-bindingBy similarity | 4 | |
Regioni | 209 – 289 | Lipid-binding and lipoprotein associationBy similarityAdd BLAST | 81 | |
Regioni | 228 – 235 | Heparin-bindingBy similarity | 8 | |
Regioni | 265 – 316 | HomooligomerizationBy similarityAdd BLAST | 52 | |
Regioni | 277 – 289 | Specificity for association with VLDLBy similarityAdd BLAST | 13 |
Sequence similaritiesi
Belongs to the apolipoprotein A1/A4/E family.Curated
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | ENOG502QVD6, Eukaryota |
Family and domain databases
InterProi | View protein in InterPro IPR000074, ApoA_E |
Pfami | View protein in Pfam PF01442, Apolipoprotein, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q7M2U8-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKVLWVALVV ALLAGCQADM EGELGSEEPL PPEQPRGQDS QPWEQVLGRL
60 70 80 90 100
WDYLRWVQTL SDQVQEELLN TQVIQELTVL MEETMKEVKA YREELEGQLA
110 120 130 140 150
PMAQETQARV SKELQAAQAR LGSDMEDLRN RLAQYRSEVQ AMLGQSTEEL
160 170 180 190 200
RARMASHLRK LRKRLLRDAD DLKKRLAVYQ AGASEGAERS VSAIRERLRP
210 220 230 240 250
LVEQSQSRAA TLSTQVGQPL LDRAEAWRQK LHGRLEEVGV RAQDRLDKMR
260 270 280 290 300
QQLEEVRSKV EEQGSQIRLQ AEAFQARLRS WFEPLVEDMQ RQWAGLVEKV
310
QLALHLSPTS PPSENH
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 258 | S → A1 Publication | 1 |
Sequence databases
PIRi | JC6549 |
Genome annotation databases
Ensembli | ENSOART00020008905; ENSOARP00020007358; ENSOARG00020005776 |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
PIRi | JC6549 |
3D structure databases
SMRi | Q7M2U8 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9940.ENSOARP00000010129 |
Genome annotation databases
Ensembli | ENSOART00020008905; ENSOARP00020007358; ENSOARG00020005776 |
Phylogenomic databases
eggNOGi | ENOG502QVD6, Eukaryota |
Family and domain databases
InterProi | View protein in InterPro IPR000074, ApoA_E |
Pfami | View protein in Pfam PF01442, Apolipoprotein, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | APOE_SHEEP | |
Accessioni | Q7M2U8Primary (citable) accession number: Q7M2U8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 16, 2004 |
Last sequence update: | December 15, 2003 | |
Last modified: | December 2, 2020 | |
This is version 69 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families