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Protein

Apolipoprotein E

Gene

Apoe

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. antioxidant activity Source: MGI
  2. beta-amyloid binding Source: UniProtKB
  3. cholesterol binding Source: GO_Central
  4. cholesterol transporter activity Source: MGI
  5. heparin binding Source: MGI
  6. hydroxyapatite binding Source: Ensembl
  7. identical protein binding Source: MGI
  8. lipid binding Source: MGI
  9. lipid transporter activity Source: MGI
  10. lipoprotein particle binding Source: MGI
  11. low-density lipoprotein particle receptor binding Source: MGI
  12. metal chelating activity Source: MGI
  13. phosphatidylcholine-sterol O-acyltransferase activator activity Source: BHF-UCL
  14. phospholipid binding Source: MGI
  15. protein homodimerization activity Source: MGI
  16. tau protein binding Source: MGI
  17. very-low-density lipoprotein particle receptor binding Source: MGI

GO - Biological processi

  1. aging Source: Ensembl
  2. alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor clustering Source: MGI
  3. artery morphogenesis Source: MGI
  4. cardiovascular system development Source: MGI
  5. cellular calcium ion homeostasis Source: MGI
  6. cellular response to cholesterol Source: Ensembl
  7. cellular response to growth factor stimulus Source: Ensembl
  8. cellular response to interleukin-1 Source: Ensembl
  9. cGMP-mediated signaling Source: MGI
  10. cholesterol biosynthetic process Source: GO_Central
  11. cholesterol catabolic process Source: MGI
  12. cholesterol efflux Source: MGI
  13. cholesterol homeostasis Source: MGI
  14. cholesterol metabolic process Source: MGI
  15. chylomicron remnant clearance Source: MGI
  16. fatty acid homeostasis Source: MGI
  17. G-protein coupled receptor signaling pathway Source: MGI
  18. high-density lipoprotein particle assembly Source: MGI
  19. high-density lipoprotein particle clearance Source: MGI
  20. high-density lipoprotein particle remodeling Source: MGI
  21. lipid homeostasis Source: MGI
  22. lipid metabolic process Source: MGI
  23. lipoprotein biosynthetic process Source: MGI
  24. lipoprotein catabolic process Source: MGI
  25. lipoprotein metabolic process Source: MGI
  26. long-chain fatty acid transport Source: MGI
  27. low-density lipoprotein particle remodeling Source: BHF-UCL
  28. maintenance of location in cell Source: MGI
  29. negative regulation of beta-amyloid formation Source: MGI
  30. negative regulation of blood coagulation Source: MGI
  31. negative regulation of blood vessel endothelial cell migration Source: MGI
  32. negative regulation of cholesterol biosynthetic process Source: MGI
  33. negative regulation of cholesterol efflux Source: MGI
  34. negative regulation of dendritic spine development Source: MGI
  35. negative regulation of dendritic spine maintenance Source: MGI
  36. negative regulation of endothelial cell proliferation Source: MGI
  37. negative regulation of inflammatory response Source: UniProtKB
  38. negative regulation of lipid biosynthetic process Source: MGI
  39. negative regulation of lipid transport across blood brain barrier Source: MGI
  40. negative regulation of MAP kinase activity Source: MGI
  41. negative regulation of neuron apoptotic process Source: GO_Central
  42. negative regulation of neuron death Source: MGI
  43. negative regulation of phospholipid efflux Source: MGI
  44. negative regulation of platelet activation Source: MGI
  45. negative regulation of postsynaptic membrane organization Source: MGI
  46. negative regulation of presynaptic membrane organization Source: MGI
  47. nitric oxide mediated signal transduction Source: MGI
  48. N-methyl-D-aspartate receptor clustering Source: MGI
  49. oligodendrocyte differentiation Source: Ensembl
  50. phospholipid efflux Source: MGI
  51. positive regulation of axon extension Source: Ensembl
  52. positive regulation of beta-amyloid formation Source: MGI
  53. positive regulation of cGMP biosynthetic process Source: MGI
  54. positive regulation of cholesterol efflux Source: MGI
  55. positive regulation of cholesterol esterification Source: BHF-UCL
  56. positive regulation of dendritic spine development Source: MGI
  57. positive regulation of dendritic spine maintenance Source: MGI
  58. positive regulation of lipid biosynthetic process Source: MGI
  59. positive regulation of lipid transport across blood brain barrier Source: MGI
  60. positive regulation of low-density lipoprotein particle receptor catabolic process Source: MGI
  61. positive regulation of membrane protein ectodomain proteolysis Source: MGI
  62. positive regulation of neurofibrillary tangle assembly Source: MGI
  63. positive regulation of neuron death Source: MGI
  64. positive regulation of nitric-oxide synthase activity Source: MGI
  65. positive regulation of phospholipid efflux Source: MGI
  66. positive regulation of postsynaptic membrane organization Source: MGI
  67. positive regulation of presynaptic membrane organization Source: MGI
  68. protein import Source: MGI
  69. receptor-mediated endocytosis Source: MGI
  70. regulation of axon extension Source: GO_Central
  71. regulation of beta-amyloid clearance Source: MGI
  72. regulation of Cdc42 protein signal transduction Source: MGI
  73. regulation of cholesterol transport Source: GO_Central
  74. regulation of gene expression Source: MGI
  75. regulation of neuron death Source: MGI
  76. regulation of tau-protein kinase activity Source: MGI
  77. response to dietary excess Source: MGI
  78. response to ethanol Source: Ensembl
  79. response to insulin Source: Ensembl
  80. response to oxidative stress Source: MGI
  81. response to retinoic acid Source: Ensembl
  82. reverse cholesterol transport Source: MGI
  83. triglyceride catabolic process Source: GO_Central
  84. triglyceride metabolic process Source: MGI
  85. vasodilation Source: MGI
  86. very-low-density lipoprotein particle clearance Source: MGI
  87. very-low-density lipoprotein particle remodeling Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Lipid transport, Transport

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_295031. Retinoid metabolism and transport.
REACT_314625. Chylomicron-mediated lipid transport.
REACT_326379. HDL-mediated lipid transport.
REACT_346699. Scavenging by Class A Receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Apolipoprotein E
Short name:
Apo-E
Gene namesi
Name:Apoe
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:88057. Apoe.

Subcellular locationi

GO - Cellular componenti

  1. blood microparticle Source: MGI
  2. chylomicron Source: MGI
  3. cytosol Source: Reactome
  4. dendrite Source: Ensembl
  5. discoidal high-density lipoprotein particle Source: Ensembl
  6. early endosome Source: Ensembl
  7. endoplasmic reticulum Source: Ensembl
  8. extracellular matrix Source: MGI
  9. extracellular region Source: Reactome
  10. extracellular space Source: MGI
  11. extracellular vesicular exosome Source: MGI
  12. extrinsic component of external side of plasma membrane Source: Ensembl
  13. Golgi apparatus Source: Ensembl
  14. high-density lipoprotein particle Source: MGI
  15. intermediate-density lipoprotein particle Source: MGI
  16. late endosome Source: Ensembl
  17. low-density lipoprotein particle Source: BHF-UCL
  18. lysosome Source: Ensembl
  19. membrane Source: MGI
  20. microtubule Source: Ensembl
  21. neuronal cell body Source: Ensembl
  22. nuclear envelope Source: Ensembl
  23. nucleus Source: MGI
  24. very-low-density lipoprotein particle Source: MGI
  25. vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chylomicron, HDL, Secreted, VLDL

Pathology & Biotechi

Disruption phenotypei

APOE single knockout mice are atherosclerosis-prone. Animals with a double knockout of APOE and CD36, fed a Western diet for 12 weeks, exhibit much lower levels of CXCL1, CXCL2 and CCL5 mRNA expression in the descending aorta and a corresponding decrease in atherosclerotic lesion formation, compared to APOE single knockout mice.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Add
BLAST
Chaini19 – 311293Apolipoprotein EPRO_0000001990Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei135 – 1351Methionine sulfoxide1 Publication
Modified residuei139 – 1391PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation sites are present in the extracellular medium.By similarity

Keywords - PTMi

Oxidation, Phosphoprotein

Proteomic databases

MaxQBiP08226.
PaxDbiP08226.
PRIDEiP08226.

PTM databases

PhosphoSiteiP08226.

Expressioni

Tissue specificityi

Secreted in plasma.

Gene expression databases

BgeeiP08226.
CleanExiMM_APOE.
ExpressionAtlasiP08226. baseline and differential.
GenevestigatoriP08226.

Interactioni

Protein-protein interaction databases

BioGridi198164. 5 interactions.
IntActiP08226. 5 interactions.
MINTiMINT-242645.

Structurei

Secondary structure

1
311
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi29 – 313Combined sources
Helixi34 – 5017Combined sources
Helixi55 – 628Combined sources
Helixi65 – 9026Combined sources
Helixi97 – 13438Combined sources
Turni135 – 1373Combined sources
Helixi141 – 17232Combined sources
Helixi184 – 1918Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YA9X-ray2.09A20-200[»]
ProteinModelPortaliP08226.
SMRiP08226. Positions 19-305.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08226.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati72 – 93221Add
BLAST
Repeati94 – 115222Add
BLAST
Repeati116 – 137223Add
BLAST
Repeati138 – 159224Add
BLAST
Repeati160 – 181225Add
BLAST
Repeati182 – 203226Add
BLAST
Repeati204 – 225227Add
BLAST
Repeati226 – 247228Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni72 – 2471768 X 22 AA approximate tandem repeatsAdd
BLAST
Regioni150 – 16011LDL receptor bindingSequence AnalysisAdd
BLAST
Regioni154 – 1574Heparin-bindingBy similarity
Regioni221 – 2288Heparin-bindingBy similarity

Sequence similaritiesi

Belongs to the apolipoprotein A1/A4/E family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG44867.
HOGENOMiHOG000034006.
HOVERGENiHBG010582.
InParanoidiP08226.
KOiK04524.
OMAiFEPIVED.
OrthoDBiEOG793B87.
PhylomeDBiP08226.
TreeFamiTF334458.

Family and domain databases

InterProiIPR000074. ApoA_E.
[Graphical view]
PfamiPF01442. Apolipoprotein. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08226-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKALWAVLLV TLLTGCLAEG EPEVTDQLEW QSNQPWEQAL NRFWDYLRWV
60 70 80 90 100
QTLSDQVQEE LQSSQVTQEL TALMEDTMTE VKAYKKELEE QLGPVAEETR
110 120 130 140 150
ARLGKEVQAA QARLGADMED LRNRLGQYRN EVHTMLGQST EEIRARLSTH
160 170 180 190 200
LRKMRKRLMR DAEDLQKRLA VYKAGAREGA ERGVSAIRER LGPLVEQGRQ
210 220 230 240 250
RTANLGAGAA QPLRDRAQAF GDRIRGRLEE VGNQARDRLE EVREHMEEVR
260 270 280 290 300
SKMEEQTQQI RLQAEIFQAR LKGWFEPIVE DMHRQWANLM EKIQASVATN
310
PIITPVAQEN Q
Length:311
Mass (Da):35,867
Last modified:August 1, 1990 - v2
Checksum:i3B36FA897CC34170
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti163 – 1631E → D in AAA37251 (PubMed:3865219).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00466 Genomic DNA. Translation: BAA00361.1.
M12414 mRNA. Translation: AAA37251.1.
BC083351 mRNA. Translation: AAH83351.1.
M73490 mRNA. Translation: AAA37252.1.
CCDSiCCDS20912.1.
PIRiJU0036.
RefSeqiNP_033826.2. NM_009696.3.
UniGeneiMm.305152.

Genome annotation databases

EnsembliENSMUST00000003066; ENSMUSP00000003066; ENSMUSG00000002985.
ENSMUST00000173739; ENSMUSP00000133371; ENSMUSG00000002985.
ENSMUST00000174064; ENSMUSP00000133302; ENSMUSG00000002985.
ENSMUST00000174355; ENSMUSP00000134160; ENSMUSG00000002985.
GeneIDi11816.
KEGGimmu:11816.
UCSCiuc009fmy.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00466 Genomic DNA. Translation: BAA00361.1.
M12414 mRNA. Translation: AAA37251.1.
BC083351 mRNA. Translation: AAH83351.1.
M73490 mRNA. Translation: AAA37252.1.
CCDSiCCDS20912.1.
PIRiJU0036.
RefSeqiNP_033826.2. NM_009696.3.
UniGeneiMm.305152.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YA9X-ray2.09A20-200[»]
ProteinModelPortaliP08226.
SMRiP08226. Positions 19-305.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198164. 5 interactions.
IntActiP08226. 5 interactions.
MINTiMINT-242645.

PTM databases

PhosphoSiteiP08226.

Proteomic databases

MaxQBiP08226.
PaxDbiP08226.
PRIDEiP08226.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003066; ENSMUSP00000003066; ENSMUSG00000002985.
ENSMUST00000173739; ENSMUSP00000133371; ENSMUSG00000002985.
ENSMUST00000174064; ENSMUSP00000133302; ENSMUSG00000002985.
ENSMUST00000174355; ENSMUSP00000134160; ENSMUSG00000002985.
GeneIDi11816.
KEGGimmu:11816.
UCSCiuc009fmy.2. mouse.

Organism-specific databases

CTDi348.
MGIiMGI:88057. Apoe.

Phylogenomic databases

eggNOGiNOG44867.
HOGENOMiHOG000034006.
HOVERGENiHBG010582.
InParanoidiP08226.
KOiK04524.
OMAiFEPIVED.
OrthoDBiEOG793B87.
PhylomeDBiP08226.
TreeFamiTF334458.

Enzyme and pathway databases

ReactomeiREACT_295031. Retinoid metabolism and transport.
REACT_314625. Chylomicron-mediated lipid transport.
REACT_326379. HDL-mediated lipid transport.
REACT_346699. Scavenging by Class A Receptors.

Miscellaneous databases

ChiTaRSiApoe. mouse.
EvolutionaryTraceiP08226.
NextBioi279703.
PROiP08226.
SOURCEiSearch...

Gene expression databases

BgeeiP08226.
CleanExiMM_APOE.
ExpressionAtlasiP08226. baseline and differential.
GenevestigatoriP08226.

Family and domain databases

InterProiIPR000074. ApoA_E.
[Graphical view]
PfamiPF01442. Apolipoprotein. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure and expression of mouse apolipoprotein E gene."
    Horiuchi K., Tajima S., Menju M., Yamamoto A.
    J. Biochem. 106:98-103(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit."
    Rajavashisth T.B., Kaptein J.S., Reue K.L., Lusis A.J.
    Proc. Natl. Acad. Sci. U.S.A. 82:8085-8089(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  4. "Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes."
    Diedrich J.F., Minnigan M., Carp R.I., Whitaker J.N., Race R., Frey W. II, Haase A.T.
    J. Virol. 65:4759-4768(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 26-311.
  5. "Mass spectral analysis of the apolipoproteins on mouse high density lipoproteins. Detection of post-translational modifications."
    Puppione D.L., Yam L.M., Bassilian S., Souda P., Castellani L.W., Schumaker V.N., Whitelegge J.P.
    Biochim. Biophys. Acta 1764:1363-1371(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 43-48; 87-100; 114-122; 130-144; 183-188; 191-198; 202-214; 226-236 AND 253-284, IDENTIFICATION BY MASS SPECTROMETRY, OXIDATION AT MET-135.
  6. Lubec G., Kang S.U.
    Submitted (MAR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 114-122, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Brain.
  7. "CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer."
    Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A., El Khoury J., Golenbock D.T., Moore K.J.
    Nat. Immunol. 11:155-161(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiAPOE_MOUSE
AccessioniPrimary (citable) accession number: P08226
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1990
Last modified: April 1, 2015
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.