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

GO curators for mouse genes have assigned the following annotations to the gene product of Lrp2. (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, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]

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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 Lrp2
  • is located in the following cellular components:
    • apical part of cell ^{[1, 11]}
    • apical plasma membrane ^{[1, 7]}
    • brush border ^[2]
    • brush border membrane ^[12]
    • coated pit ^[1]
    • endocytic vesicle ^[1]
    • endoplasmic reticulum ^[1]
    • endosome ^{[2, 4]}
    • Golgi apparatus ^[1]
    • membrane ^[5]
• The gene product of Lrp2 has been shown to bind to the gene products of Dab1, Dlg4, Gipc1, Lrp2bp, Mapk8ip1, Mapk8ip2, Sorl1. ^{[3, 8, 10]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Lrp2
  • participates in the following biological processes:
    • cell proliferation ^[9]
    • forebrain development ^[9]
    • receptor-mediated endocytosis ^[6]
    • vitamin metabolic process ^[6]

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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 Lrp2:
  • participates in the following biological processes:
    • endosomal transport
    • hemoglobin import
    • hormone secretion
    • lipoprotein transport
    • receptor-mediated endocytosis
    • response to X-ray
    • transcytosis
  • performs the following molecular functions:
    • hemoglobin binding
    • lipoprotein transporter activity
    • receptor activity
  • is located in the following cellular components:
    • apical plasma membrane
    • brush border
    • brush border membrane
    • cytoplasm
    • endosome
    • extracellular space
    • membrane

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Summary text based on GO annotations supported by structural data

• Lrp2 encodes a protein or proteins that contain the following InterPro domains: EGF-like calcium-binding, EGF-like calcium-binding, conserved site, EGF-like, conserved site, EGF-type aspartate/asparagine hydroxylation site, Epidermal growth factor-like domain, Growth factor, receptor, LDLR class B repeat, Low-density lipoprotein (LDL) receptor class A repeat, Low-density lipoprotein (LDL) receptor class A, conserved site, Six-bladed beta-propeller, TolB-like, indicating that the gene product:
  • performs the following molecular functions:
    • calcium ion binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Lrp2 indicates that it:
  • participates in the following biological processes:
    • endocytosis
  • performs the following molecular functions:
    • metal ion binding
    • SH3 domain binding
  • is located in the following cellular components:
    • integral to membrane

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References

1. Assemat E et al. (2005) Expression and role of cubilin in the internalization of nutrients during the peri-implantation development of the rodent embryo. Biol Reprod, 72:1079-86. (PubMed:15616221)
2. Christensen EI et al. (2003) Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci U S A, 100:8472-7. (PubMed:12815097)
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. Hammad SM et al. (2000) Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J Biol Chem, 275:12003-8. (PubMed:10766831)
5. 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)
6. Nykjaer A et al. (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell, 96:507-15. (PubMed:10052453)
7. Pernot E et al. (2011) The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system. Pflugers Arch, 462:871-83. (PubMed:21938401)
8. Petersen HH et al. (2003) Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule. J Cell Sci, 116:453-61. (PubMed:12508107)
9. Spoelgen R et al. (2005) LRP2/megalin is required for patterning of the ventral telencephalon. Development, 132:405-14. (PubMed:15623804)
10. 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)
11. Strope S et al. (2004) Mouse amnionless, which is required for primitive streak assembly, mediates cell-surface localization and endocytic function of cubilin on visceral endoderm and kidney proximal tubules. Development, 131:4787-95. (PubMed:15342463)
12. van Hoek AN et al. (2000) Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney. Am J Physiol Renal Physiol, 278:F310-6. (PubMed:10662735)

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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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