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

GO curators for mouse genes have assigned the following annotations to the gene product of Ldlr. (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 low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. Low density lipoprotein (LDL) is normally bound at the cell membrane and taken into the cell ending up in lysosomes where the protein is degraded and the cholesterol is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 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 Ldlr
  • participates in the following biological processes:
    • lipoprotein catabolic process ^[5]
  • performs the following molecular functions:
    • low-density lipoprotein particle binding ^{[5, 9]}
    • low-density lipoprotein receptor activity ^[4]
    • very-low-density lipoprotein particle receptor activity ^[2]
  • is located in the following cellular components:
    • endosome ^[3]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Ldlr
  • participates in the following biological processes:
    • cholesterol homeostasis ^{[3, 10]}
    • cholesterol import ^[6]
    • cholesterol metabolic process ^[13]
    • cholesterol transport ^[12]
    • lipoprotein catabolic process ^{[7, 10]}
    • low-density lipoprotein particle clearance ^[6]
    • phospholipid transport ^[6]
    • positive regulation of triglyceride biosynthetic process ^[6]
    • regulation of phosphatidylcholine catabolic process ^[6]
  • performs the following molecular functions:
    • low-density lipoprotein receptor activity ^[12]
• Researchers have inferred, based on genetic interactions, that the gene product of Ldlr
  • participates in the following biological processes:
    • cholesterol homeostasis based on interactions with Apob ^[11]
    • lipid metabolic process based on interactions with Apob ^[11]
    • lipoprotein metabolic process based on interactions with Apob ^{[1, 11]}

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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 Ldlr:
  • participates in the following biological processes:
    • cholesterol homeostasis
    • cholesterol transport
    • endocytosis
    • intestinal cholesterol absorption
    • low-density lipoprotein particle clearance
  • performs the following molecular functions:
    • glycoprotein binding
    • low-density lipoprotein receptor activity
    • very-low-density lipoprotein particle receptor activity
  • is located in the following cellular components:
    • caveola
    • cell surface
    • coated pit
    • early endosome
    • external side of plasma membrane
    • Golgi apparatus
    • late endosome
    • lysosome
    • plasma membrane
    • recycling endosome membrane

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Summary text based on GO annotations supported by structural data

• Ldlr 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 Ldlr indicates that it:
  • participates in the following biological processes:
    • lipid transport
    • steroid metabolic process
    • transport
  • is located in the following cellular components:
    • integral to membrane
    • low-density lipoprotein particle
    • membrane

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References

1. 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)
2. Grosskopf I et al. (2005) Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceride-rich lipoproteins and removal of their remnants. Arterioscler Thromb Vasc Biol, 25:2573-9. (PubMed:16166565)
3. Jones C et al. (2003) Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. J Biol Chem, 278:29024-30. (PubMed:12746448)
4. Kulinski A et al. (2002) Microsomal Triacylglycerol Transfer Protein Is Required for Lumenal Accretion of Triacylglycerol Not Associated with ApoB, as Well as for ApoB Lipidation. J Biol Chem, 277:31516-25. (PubMed:12072432)
5. Lalanne F et al. (2005) Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells. J Lipid Res, 46:1312-9. (PubMed:15741654)
6. Minahk C et al. (2008) Conversion of low density lipoprotein-associated phosphatidylcholine to triacylglycerol by primary hepatocytes. J Biol Chem, 283:6449-58. (PubMed:18175806)
7. Rashid S et al. (2005) Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A, 102:5374-9. (PubMed:15805190)
8. Stockinger W et al. (2002) The PX-domain protein SNX17 interacts with members of the LDL receptor family and modulates endocytosis of the LDL receptor. EMBO J, 21:4259-67. (PubMed:12169628)
9. van Ree JH et al. (1995) Increased response to cholesterol feeding in apolipoprotein C1-deficient mice. Biochem J, 305:905-11. (PubMed:7848292)
10. 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)
11. Veniant MM et al. (2000) Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100 J Clin Invest, 106:1501-10. (PubMed:11120757)
12. Wang MD et al. (2007) Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res, 48:633-45. (PubMed:17148552)
13. Zabalawi M et al. (2007) Inflammation and skin cholesterol in LDLr-/-, apoA-I-/- mice: link between cholesterol homeostasis and self-tolerance? J Lipid Res, 48:52-65. (PubMed:17071966)

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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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