Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Apoe. (This text reflects annotations as of Tuesday, May 21, 2013.)

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis in the liver. Apolipoprotein E, a main apoprotein of the chylomicron, binds to a specific receptor on liver cells and peripheral cells. ApoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and APOC2. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jul 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Apoe
  • participates in the following biological processes:
    • cellular calcium ion homeostasis ^[6]
    • cholesterol efflux ^[8]
  • performs the following molecular functions:
    • cholesterol transporter activity ^[8]
    • lipoprotein particle binding ^[14]
  • is located in the following cellular components:
    • extracellular space ^{[5, 8, 13, 18]}
    • low-density lipoprotein particle ^[20]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Apoe
  • participates in the following biological processes:
    • cardiovascular system development ^[4]
    • cholesterol catabolic process ^[1]
    • cholesterol efflux ^[7]
    • cholesterol homeostasis ^{[5, 11]}
    • cholesterol metabolic process ^{[11, 12]}
    • lipid homeostasis ^[19]
    • lipoprotein catabolic process ^[19]
    • lipoprotein metabolic process ^[16]
    • low-density lipoprotein particle remodeling ^[20]
    • maintenance of location in cell ^[19]
    • positive regulation of catalytic activity ^[20]
    • positive regulation of cholesterol esterification ^[20]
    • regulation of gene expression ^[19]
    • response to dietary excess ^[19]
    • response to oxidative stress ^[10]
    • vasodilation ^[1]
    • very-low-density lipoprotein particle remodeling ^[20]
  • performs the following molecular functions:
    • phosphatidylcholine-sterol O-acyltransferase activator activity ^[20]
• Researchers have inferred, based on genetic interactions, that the gene product of Apoe
  • participates in the following biological processes:
    • artery morphogenesis based on interactions with Apob ^[15]
    • cholesterol homeostasis based on interactions with Apob ^{[15, 17]}
    • lipid metabolic process based on interactions with Apob ^[17]
    • lipoprotein biosynthetic process based on interactions with Apoa1 ^[2]
    • lipoprotein metabolic process based on interactions with Apob ^{[3, 17]}
    • negative regulation of inflammatory response based on interactions with Zfp36 ^[9]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Apoe:
  • participates in the following biological processes:
    • aging
    • cGMP-mediated signaling
    • cholesterol efflux
    • cholesterol homeostasis
    • cholesterol metabolic process
    • chylomicron remnant clearance
    • G-protein coupled receptor signaling pathway
    • high-density lipoprotein particle assembly
    • high-density lipoprotein particle clearance
    • high-density lipoprotein particle remodeling
    • lipid transport
    • lipoprotein metabolic process
    • negative regulation of apoptotic process
    • negative regulation of blood coagulation
    • negative regulation of blood vessel endothelial cell migration
    • negative regulation of cholesterol biosynthetic process
    • negative regulation of endothelial cell proliferation
    • negative regulation of MAP kinase activity
    • negative regulation of neuron apoptotic process
    • negative regulation of platelet activation
    • nitric oxide mediated signal transduction
    • phospholipid efflux
    • positive regulation of axon extension
    • positive regulation of cGMP biosynthetic process
    • positive regulation of cholesterol efflux
    • positive regulation of cholesterol esterification
    • positive regulation of low-density lipoprotein particle receptor catabolic process
    • positive regulation of membrane protein ectodomain proteolysis
    • positive regulation of nitric-oxide synthase activity
    • receptor-mediated endocytosis
    • regulation of Cdc42 protein signal transduction
    • reverse cholesterol transport
    • triglyceride metabolic process
    • very-low-density lipoprotein particle clearance
    • very-low-density lipoprotein particle remodeling
  • performs the following molecular functions:
    • antioxidant activity
    • beta-amyloid binding
    • heparin binding
    • hydroxyapatite binding
    • identical protein binding
    • lipid binding
    • lipid transporter activity
    • low-density lipoprotein particle receptor binding
    • metal chelating activity
    • phosphatidylcholine-sterol O-acyltransferase activator activity
    • phospholipid binding
    • protein heterodimerization activity
    • protein homodimerization activity
    • tau protein binding
    • very-low-density lipoprotein particle receptor binding
  • is located in the following cellular components:
    • chylomicron
    • cytoplasm
    • dendrite
    • early endosome
    • extracellular space
    • extrinsic to external side of plasma membrane
    • Golgi apparatus
    • high-density lipoprotein particle
    • intermediate-density lipoprotein particle
    • late endosome
    • low-density lipoprotein particle
    • microtubule
    • neuronal cell body
    • plasma membrane
    • very-low-density lipoprotein particle

---

Summary text based on GO annotations supported by structural data

• Apoe encodes a protein or proteins that contain the following InterPro domains: Apolipoprotein, Apolipoprotein A1/A4/E, indicating that the gene product:
  • is located in the following cellular components:
    • extracellular region

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Apoe indicates that it:
  • participates in the following biological processes:
    • transport
  • is located in the following cellular components:
    • extracellular region

---

References

1. Barton M et al. (1998) Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A, 95:14367-72. (PubMed:9826706)
2. Cabana VG et al. (2004) Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro. J Lipid Res, 45:317-25. (PubMed:14595002)
3. Chen Z et al. (2004) Hepatic secretion of apoB-100 is impaired in hypobetalipoproteinemic mice with an apoB-38.9-specifying allele. J Lipid Res, 45:155-63. (PubMed:13130124)
4. Elia L et al. (2009) The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ, 16:1590-8. (PubMed:19816508)
5. Goodrum JF et al. (1995) Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-I in mice. J Neurochem, 64:408-16. (PubMed:7798939)
6. Hartmann H et al. (1994) Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity. Biochem Biophys Res Commun, 200:1185-92. (PubMed:8185566)
7. Hirano T et al. (2001) Apoprotein C-III deficiency markedly stimulates triglyceride secretion in vivo: comparison with apoprotein E. Am J Physiol Endocrinol Metab, 281:E665-9. (PubMed:11551841)
8. Hirsch-Reinshagen V et al. (2004) Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J Biol Chem, 279:41197-207. (PubMed:15269218)
9. Kang JG et al. (2011) Zinc finger protein tristetraprolin interacts with CCL3 mRNA and regulates tissue inflammation. J Immunol, 187:2696-701. (PubMed:21784977)
10. Matthews RT et al. (1996) Increased 3-nitrotyrosine in brains of Apo E-deficient mice. Brain Res, 718:181-4. (PubMed:8773783)
11. Plump AS et al. (1992) Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell, 71:343-53. (PubMed:1423598)
12. Plump AS et al. (1996) Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production. J Clin Invest, 97:2660-71. (PubMed:8647961)
13. Plump AS et al. (1997) ApoA-I knockout mice: characterization of HDL metabolism in homozygotes and identification of a post-RNA mechanism of apoA-I up-regulation in heterozygotes. J Lipid Res, 38:1033-47. (PubMed:9186920)
14. Raffai RL et al. (2001) Introduction of human apolipoprotein E4 'domain interaction' into mouse apolipoprotein E. Proc Natl Acad Sci U S A, 98:11587-91. (PubMed:11553788)
15. Tirziu D et al. (2005) Delayed arteriogenesis in hypercholesterolemic mice. Circulation, 112:2501-9. (PubMed:16230502)
16. Veniant MM et al. (1998) Lipoprotein clearance mechanisms in LDL receptor-deficient Apo-B48-only and Apo-B100-only mice. J Clin Invest, 102:1559-68. (PubMed:9788969)
17. Veniant MM et al. (2000) Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100 J Clin Invest, 106:1501-10. (PubMed:11120757)
18. Webb NR et al. (1997) Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice. J Lipid Res, 38:1583-90. (PubMed:9300780)
19. Wu D et al. (2007) Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages. J Lipid Res, 48:2571-8. (PubMed:17720994)
20. Zhao Y et al. (2005) Apolipoprotein E is the major physiological activator of lecithin-cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins. Biochemistry, 44:1013-25. (PubMed:15654758)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---