UniProtKB - P18649 (APOE_CANLF)
Protein
Apolipoprotein E
Gene
APOE
Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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: UniProtKB
- heparan sulfate proteoglycan binding Source: UniProtKB
- heparin binding Source: UniProtKB
- identical protein binding Source: UniProtKB
- lipid binding Source: UniProtKB-KW
- low-density lipoprotein particle receptor binding Source: UniProtKB
- very-low-density lipoprotein particle receptor binding Source: GO_Central
GO - Biological processi
- cholesterol catabolic process Source: GO_Central
- cholesterol efflux Source: UniProtKB
- chylomicron remnant clearance Source: UniProtKB
- high-density lipoprotein particle assembly Source: UniProtKB
- intermediate-density lipoprotein particle clearance Source: UniProtKB
- lipoprotein biosynthetic process Source: UniProtKB
- lipoprotein catabolic process Source: GO_Central
- negative regulation of amyloid fibril formation Source: UniProtKB
- negative regulation of neuron apoptotic process Source: GO_Central
- positive regulation of amyloid-beta clearance Source: UniProtKB
- positive regulation of nitric-oxide synthase activity Source: GO_Central
- regulation of amyloid-beta clearance Source: GO_Central
- triglyceride-rich lipoprotein particle clearance Source: UniProtKB
- very-low-density lipoprotein particle clearance Source: UniProtKB
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 | Canis lupus familiaris (Dog) (Canis familiaris) |
Taxonomic identifieri | 9615 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › |
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
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
- very-low-density lipoprotein particle Source: UniProtKB
Keywords - Cellular componenti
Chylomicron, Extracellular matrix, HDL, Secreted, VLDLPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | 1 PublicationAdd BLAST | 18 | |
ChainiPRO_0000191636 | 19 – 323 | Apolipoprotein EAdd BLAST | 305 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 149 | Methionine sulfoxideBy similarity | 1 | |
Modified residuei | 153 | 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, PhosphoproteinProteomic databases
PaxDbi | P18649 |
PRIDEi | P18649 |
Expressioni
Gene expression databases
Bgeei | ENSCAFG00000004617, Expressed in liver and 50 other tissues |
Interactioni
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
- very-low-density lipoprotein particle receptor binding Source: GO_Central
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000006888 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 86 – 107 | 1Add BLAST | 22 | |
Repeati | 108 – 129 | 2Add BLAST | 22 | |
Repeati | 130 – 151 | 3Add BLAST | 22 | |
Repeati | 152 – 173 | 4Add BLAST | 22 | |
Repeati | 174 – 195 | 5Add BLAST | 22 | |
Repeati | 196 – 217 | 6Add BLAST | 22 | |
Repeati | 218 – 239 | 7Add BLAST | 22 | |
Repeati | 240 – 261 | 8Add BLAST | 22 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 86 – 261 | 8 X 22 AA approximate tandem repeatsAdd BLAST | 176 | |
Regioni | 164 – 174 | LDL and other lipoprotein receptors bindingBy similarityAdd BLAST | 11 | |
Regioni | 168 – 171 | Heparin-bindingBy similarity | 4 | |
Regioni | 216 – 296 | Lipid-binding and lipoprotein associationBy similarityAdd BLAST | 81 | |
Regioni | 235 – 242 | Heparin-bindingBy similarity | 8 | |
Regioni | 272 – 323 | HomooligomerizationBy similarityAdd BLAST | 52 | |
Regioni | 284 – 296 | 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 |
HOGENOMi | CLU_066029_0_0_1 |
InParanoidi | P18649 |
OMAi | ARLKGWF |
OrthoDBi | 1314660at2759 |
TreeFami | TF334458 |
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
P18649-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKVLWAALVV TLLAGCWADV QPEPELEREL EPKVQQELEP EAGWQTGQPW
60 70 80 90 100
EAALARFWDY LRWVQTLSDQ VQEGVLNTQV TQELTALMDE TMKEVKAYKA
110 120 130 140 150
ELDEQLGPMT SETQARVAKE LQAAQARLRS DMEDVRNRLT QYRGELQAML
160 170 180 190 200
GQSSEELRAR FASHMRKLRK RVLRDAEDLQ RRLAVYKAGV REGAERSVSS
210 220 230 240 250
IRERLWPLLE QARERNAKVG ALATQPLLER ADALGQQLRG QLEEMSSRAR
260 270 280 290 300
GHLEEMREQI QEVRVKMEEQ ADQIRQKAEA FQARLKSWFE PLLEDMQRQW
310 320
DGLVEKVQAA VATIPTSKPV EEP
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 130 | S → A (PubMed:2515239).Curated | 1 | |
Sequence conflicti | 234 | L → W (PubMed:2515239).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AAEX03000895 Genomic DNA No translation available. |
PIRi | A05310 C60940 |
RefSeqi | XP_005616517.2, XM_005616460.2 XP_533644.1, XM_533644.5 XP_866043.1, XM_860950.3 |
Genome annotation databases
GeneIDi | 476438 |
KEGGi | cfa:476438 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AAEX03000895 Genomic DNA No translation available. |
PIRi | A05310 C60940 |
RefSeqi | XP_005616517.2, XM_005616460.2 XP_533644.1, XM_533644.5 XP_866043.1, XM_860950.3 |
3D structure databases
SMRi | P18649 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000006888 |
Proteomic databases
PaxDbi | P18649 |
PRIDEi | P18649 |
Genome annotation databases
GeneIDi | 476438 |
KEGGi | cfa:476438 |
Organism-specific databases
CTDi | 348 |
Phylogenomic databases
eggNOGi | ENOG502QVD6, Eukaryota |
HOGENOMi | CLU_066029_0_0_1 |
InParanoidi | P18649 |
OMAi | ARLKGWF |
OrthoDBi | 1314660at2759 |
TreeFami | TF334458 |
Gene expression databases
Bgeei | ENSCAFG00000004617, Expressed in liver and 50 other tissues |
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_CANLF | |
Accessioni | P18649Primary (citable) accession number: P18649 Secondary accession number(s): F1PJ74 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1990 |
Last sequence update: | December 11, 2019 | |
Last modified: | December 2, 2020 | |
This is version 115 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families