Low density lipoprotein receptor-related protein 2
Mutations in LRP2 gene cause autosomal recessive Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).
Protein Structure
Megalin, the product of the LRP2 gene, belongs to the LDL receptor family. I consists of a huge extracellular domain (4398 amino acids), a single transmembrane segment, and a short cytoplsmatic tail (209). The extracellular domain contains 36 cysteine-rich complement-type repeats in four clusters, 16 growth factor repeats separated by 8 YWTD spacers, and a single epidermal growth factor-like repeat. The intracellular domain contains 2 endocytic motifs (NPXY), 1 NPXY-like motif (NQNY), 1 SH3 domain, 1 PDZ domain, and phosphorylation sites.
Genetests:
Related Diseases:
References:
1. |
Chatelet F et al. (1986) Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. II. Extrarenal distribution.
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2. |
Saito A et al. (2010) Molecular mechanisms of receptor-mediated endocytosis in the renal proximal tubular epithelium.
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3. |
Kantarci S et al. (2007) Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes.
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4. |
Caruso-Neves C et al. (2006) PKB and megalin determine the survival or death of renal proximal tubule cells.
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5. |
Naccache SN et al. (2006) Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.
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6. |
Hammes A et al. (2005) Role of endocytosis in cellular uptake of sex steroids.
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7. |
Tramontano A et al. (2004) Conformation and glycosylation of a megalin fragment correlate with nephritogenicity in Heymann nephritis.
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8. |
Nagai M et al. (2003) The adaptor protein ARH escorts megalin to and through endosomes.
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9. |
Chassaing N et al. (2003) Donnai-Barrow syndrome: four additional patients.
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10. |
Nykjaer A et al. (2001) Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).
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11. |
Schmitz C et al. (2002) Megalin deficiency offers protection from renal aminoglycoside accumulation.
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12. |
Leheste JR et al. (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria.
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13. |
Marinò M et al. (1999) Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis.
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14. |
Nykjaer A et al. (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.
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15. |
Willnow TE et al. (1996) Defective forebrain development in mice lacking gp330/megalin.
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16. |
Raychowdhury R et al. (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor.
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17. |
Kerjaschki D et al. (1983) Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats.
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18. |
Moestrup SK et al. (1995) Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs.
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19. |
Farquhar MG et al. (1995) The Heymann nephritis antigenic complex: megalin (gp330) and RAP.
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20. |
Chowdhary BP et al. (1995) In situ hybridization mapping of a 500-kDa calcium-sensing protein gene (LRP2) to human chromosome region 2q31>q32.1 and porcine chromosome region 15q22>q24.
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21. |
None (1995) The unfolding story of megalin (gp330): now recognized as a drug receptor.
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22. |
Kounnas MZ et al. (1995) Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin.
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23. |
Saito A et al. (1994) Complete cloning and sequencing of rat gp330/"megalin," a distinctive member of the low density lipoprotein receptor gene family.
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24. |
Korenberg JR et al. (1994) Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1).
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25. |
Donnai D et al. (1993) Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder?
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26. |
Hjälm G et al. (1996) Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties.
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27. |
Devriendt K et al. (1998) Proteinuria in a patient with the diaphragmatic hernia-hypertelorism-myopia-deafness syndrome: further evidence that the facio-oculo-acoustico-renal syndrome represents the same entity.
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28. |
OMIM.ORG article
Omim 600073
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29. |
NCBI article
NCBI 4036
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30. |
Orphanet article
Orphanet ID 159747
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31. |
Wikipedia article
Wikipedia EN (LRP2)
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Update: Aug. 14, 2020