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

GO curators for mouse genes have assigned the following annotations to the gene product of Lrp1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is an endocytic receptor involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the A2M-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer patients. [provided by RefSeq, Jan 2010]

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

• Researchers have inferred from direct assay, that the gene product of Lrp1
  • participates in the following biological processes:
    • negative regulation of Wnt receptor signaling pathway ^[5]
    • receptor-mediated endocytosis ^[11]
  • performs the following molecular functions:
    • calcium ion binding ^[4]
  • is located in the following cellular components:
    • integral to plasma membrane ^[4]
    • membrane ^[9]
• The gene product of Lrp1 has been shown to bind to the gene products of A2m, Dab1, Dlg4, Ldlrap1, Lrp1, Mapk8ip1, Mapk8ip2, Pid1. ^{[2, 3, 6, 7, 8, 12]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Lrp1
  • participates in the following biological processes:
    • aorta morphogenesis ^[13]
    • apoptotic cell clearance ^[10]
    • beta-amyloid clearance ^[1]
    • cholesterol metabolic process ^[7]
    • negative regulation of platelet-derived growth factor receptor-beta signaling pathway ^[13]
    • negative regulation of smooth muscle cell migration ^[13]
    • positive regulation of cholesterol efflux ^[14]
    • positive regulation of lipid transport ^[14]
    • regulation of actin cytoskeleton organization ^[13]
    • regulation of cholesterol transport ^[14]
    • regulation of phospholipase A2 activity ^[14]

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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 Lrp1:
  • participates in the following biological processes:
    • cell proliferation
    • negative regulation of neuron apoptotic process
    • positive regulation of protein transport
    • protein kinase C-activating G-protein coupled receptor signaling pathway
    • receptor-mediated endocytosis
  • performs the following molecular functions:
    • apolipoprotein binding
    • protease binding
    • protein complex binding
  • is located in the following cellular components:
    • clathrin-coated vesicle
    • dendrite
    • endosome
    • neuronal cell body
    • perinuclear region of cytoplasm

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Lrp1 indicates that it:
  • participates in the following biological processes:
    • endocytosis
    • multicellular organismal development
  • performs the following molecular functions:
    • metal ion binding
  • is located in the following cellular components:
    • coated pit
    • cytoplasm
    • integral to membrane
    • nucleus
    • plasma membrane

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References

1. Bell RD et al. (2009) SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat Cell Biol, 11:143-53. (PubMed:19098903)
2. Fernandez E et al. (2009) Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. Mol Syst Biol, 5:269. (PubMed:19455133)
3. Gotthardt M et al. (2000) Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J Biol Chem, 275:25616-24. (PubMed:10827173)
4. Herz J et al. (1988) Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO J, 7:4119-27. (PubMed:3266596)
5. Johnson EB et al. (2005) Abnormal development of the apical ectodermal ridge and polysyndactyly in Megf7-deficient mice. Hum Mol Genet, 14:3523-38. (PubMed:16207730)
6. Kajiwara Y et al. (2010) Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease. Mol Neurodegener, 5:1. (PubMed:20205790)
7. Liu Q et al. (2007) Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron, 56:66-78. (PubMed:17920016)
8. Mameza MG et al. (2007) Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions. J Neurochem, 103:927-41. (PubMed:17727637)
9. Marschang P et al. (2004) Normal development and fertility of knockout mice lacking the tumor suppressor gene LRP1b suggest functional compensation by LRP1. Mol Cell Biol, 24:3782-93. (PubMed:15082773)
10. Monks J et al. (2005) Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ, 12:107-14. (PubMed:15647754)
11. Ranganathan S et al. (2011) LRAD3, A Novel Low-Density Lipoprotein Receptor Family Member That Modulates Amyloid Precursor Protein Trafficking. J Neurosci, 31:10836-10846. (PubMed:21795536)
12. Spoelgen R et al. (2009) Interaction of the apolipoprotein E receptors low density lipoprotein receptor-related protein and sorLA/LR11. Neuroscience, 158:1460-8. (PubMed:19047013)
13. Zhou L et al. (2009) LRP1 regulates architecture of the vascular wall by controlling PDGFRbeta-dependent phosphatidylinositol 3-kinase activation. PLoS One, 4:e6922. (PubMed:19742316)
14. Zhou L et al. (2009) LRP1 controls cPLA2 phosphorylation, ABCA1 expression and cellular cholesterol export. PLoS One, 4:e6853. (PubMed:19718435)

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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

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