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Gene Review

LRP2  -  low density lipoprotein receptor-related...

Homo sapiens

Synonyms: DBS, GP330, Glycoprotein 330, LRP-2, Low-density lipoprotein receptor-related protein 2, ...
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Disease relevance of LRP2


High impact information on LRP2


Chemical compound and disease context of LRP2


Biological context of LRP2


Anatomical context of LRP2

  • Ligand blotting of rabbit kidney cortex with rabbit 125I-TC-B12 and human TC-57Co-B12 revealed an exclusive binding to megalin, a 600-kDa endocytic receptor present in renal proximal tubule epithelium and other absorptive epithelia [8].
  • 125I-TC-B12 was efficiently endocytosed in a RAP-inhibitable manner in megalin-expressing rat yolk sac carcinoma cells and in vivo microperfused rat proximal tubules [8].
  • Megalin is the major receptor in absorptive epithelial cells of the proximal tubules and an antigenic determinant for Heymann nephritis in rats [9].
  • Several cultured cell lines that express gp330 and ones that do not express the receptor were examined for their ability to bind and internalize 125I-apoJ [10].
  • To identify ligands specific for gp330 and relevant to its localization on epithelia such as in the mammary gland, gp330-Sepharose affinity chromatography was performed [10].

Associations of LRP2 with chemical compounds


Physical interactions of LRP2

  • In this report, we tested several other LRP ligands for their ability to interact with human and rat gp330 in vitro [15].
  • However, we found that gp330 (purified from human or rat) bound the lipolytic enzyme lipoprotein lipase (LPL) with high affinity (Kd = 6.1 and 2.7 nM, respectively) [15].
  • The binding of beta2-glycoprotein-I and beta2-glycoprotein-I- phospholipid complexes to megalin was completely blocked by receptor-associated protein [12].
  • Circulating thyroglobulin transcytosed by thyroid cells in complexed with secretory components of its endocytic receptor megalin [16].
  • Taken together, these findings indicate that a significant pool of NHE3 exists as a multimeric complex with megalin in the brush border of the proximal tubule [17].

Regulatory relationships of LRP2


Other interactions of LRP2

  • We recently demonstrated that gp330 and LRP may be functionally related as well; both bind the 39-kDa polypeptide referred to as receptor-associated protein (Kounnas, M. Z., Argraves, W. S., and Strickland, D. K. (1992) J. Biol. Chem. 267, 21162-21166) [15].
  • Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin [10].
  • The findings support the possibility that LRP-2 can act in vivo to mediate clearance of the complex from biological fluids such as cerebrospinal fluid and thereby play a role in the regulation of Abeta accumulation [21].
  • This autoantibody may modulate the function of CD69- and LRP2-expressing cells [1].
  • These findings indicate that gp330, like other LDLR family members, mediates endocytosis of its ligands [22].

Analytical, diagnostic and therapeutic context of LRP2


  1. Anti-CD69 autoantibodies cross-react with low density lipoprotein receptor-related protein 2 in systemic autoimmune diseases. Yu, X., Matsui, T., Otsuka, M., Sekine, T., Yamamoto, K., Nishioka, K., Kato, T. J. Immunol. (2001) [Pubmed]
  2. Autoantibodies to low-density-lipoprotein-receptor-related protein 2 (LRP2) in systemic autoimmune diseases. Ooka, S., Matsui, T., Nishioka, K., Kato, T. Arthritis Res. Ther. (2003) [Pubmed]
  3. Megalin-mediated endocytosis of vitamin d binding protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. Rowling, M.J., Kemmis, C.M., Taffany, D.A., Welsh, J. J. Nutr. (2006) [Pubmed]
  4. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). Nykjaer, A., Fyfe, J.C., Kozyraki, R., Leheste, J.R., Jacobsen, C., Nielsen, M.S., Verroust, P.J., Aminoff, M., de la Chapelle, A., Moestrup, S.K., Ray, R., Gliemann, J., Willnow, T.E., Christensen, E.I. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Megalin and cubilin: multifunctional endocytic receptors. Christensen, E.I., Birn, H. Nat. Rev. Mol. Cell Biol. (2002) [Pubmed]
  6. Truncated apo B-70.5-containing lipoproteins bind to megalin but not the LDL receptor. Chen, Z., Saffitz, J.E., Latour, M.A., Schonfeld, G. J. Clin. Invest. (1999) [Pubmed]
  7. Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen. Striekland, D.K., Ashcom, J.D., Williams, S., Battey, F., Behre, E., McTigue, K., Battey, J.F., Argraves, W.S. J. Biol. Chem. (1991) [Pubmed]
  8. Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis. Moestrup, S.K., Birn, H., Fischer, P.B., Petersen, C.M., Verroust, P.J., Sim, R.B., Christensen, E.I., Nexø, E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. The mammalian low-density lipoprotein receptor family. Hussain, M.M., Strickland, D.K., Bakillah, A. Annu. Rev. Nutr. (1999) [Pubmed]
  10. Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. Kounnas, M.Z., Loukinova, E.B., Stefansson, S., Harmony, J.A., Brewer, B.H., Strickland, D.K., Argraves, W.S. J. Biol. Chem. (1995) [Pubmed]
  11. Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes. Andreasen, P.A., Sottrup-Jensen, L., Kjøller, L., Nykjaer, A., Moestrup, S.K., Petersen, C.M., Gliemann, J. FEBS Lett. (1994) [Pubmed]
  12. beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin. Moestrup, S.K., Schousboe, I., Jacobsen, C., Leheste, J.R., Christensen, E.I., Willnow, T.E. J. Clin. Invest. (1998) [Pubmed]
  13. The Heymann nephritis antigenic complex: megalin (gp330) and RAP. Farquhar, M.G., Saito, A., Kerjaschki, D., Orlando, R.A. J. Am. Soc. Nephrol. (1995) [Pubmed]
  14. The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes. Patrie, K.M., Drescher, A.J., Goyal, M., Wiggins, R.C., Margolis, B. J. Am. Soc. Nephrol. (2001) [Pubmed]
  15. Glycoprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro. Kounnas, M.Z., Chappell, D.A., Strickland, D.K., Argraves, W.S. J. Biol. Chem. (1993) [Pubmed]
  16. Circulating thyroglobulin transcytosed by thyroid cells in complexed with secretory components of its endocytic receptor megalin. Marinò, M., Chiovato, L., Mitsiades, N., Latrofa, F., Andrews, D., Tseleni-Balafouta, S., Collins, A.B., Pinchera, A., McCluskey, R.T. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  17. Specific association of megalin and the Na+/H+ exchanger isoform NHE3 in the proximal tubule. Biemesderfer, D., Nagy, T., DeGray, B., Aronson, P.S. J. Biol. Chem. (1999) [Pubmed]
  18. Cubilin, a multifunctional epithelial receptor: an overview. Kozyraki, R. J. Mol. Med. (2001) [Pubmed]
  19. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. Hvidberg, V., Jacobsen, C., Strong, R.K., Cowland, J.B., Moestrup, S.K., Borregaard, N. FEBS Lett. (2005) [Pubmed]
  20. Cubilin and megalin in radiation-induced renal injury with labelled somatostatin analogues: are we just dealing with the kidney? Rolleman, E.J., Valkema, R., Melis, M., Krenning, E.P., Visser, T.J., de Jong, M. Eur. J. Nucl. Med. Mol. Imaging (2006) [Pubmed]
  21. Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. Hammad, S.M., Ranganathan, S., Loukinova, E., Twal, W.O., Argraves, W.S. J. Biol. Chem. (1997) [Pubmed]
  22. gp330 on type II pneumocytes mediates endocytosis leading to degradation of pro-urokinase, plasminogen activator inhibitor-1 and urokinase-plasminogen activator inhibitor-1 complex. Stefansson, S., Kounnas, M.Z., Henkin, J., Mallampalli, R.K., Chappell, D.A., Strickland, D.K., Argraves, W.S. J. Cell. Sci. (1995) [Pubmed]
  23. Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1). Korenberg, J.R., Argraves, K.M., Chen, X.N., Tran, H., Strickland, D.K., Argraves, W.S. Genomics (1994) [Pubmed]
  24. Megalin-dependent internalization of cadmium-metallothionein and cytotoxicity in cultured renal proximal tubule cells. Wolff, N.A., Abouhamed, M., Verroust, P.J., Thévenod, F. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  25. Degradation of urokinase plasminogen activator (UPA) in endometrial stromal cells requires both the UPA receptor and the low-density lipoprotein receptor-related protein/alpha2-macroglobulin receptor. Casslén, B., Gustavsson, B., Angelin, B., Gåfvels, M. Mol. Hum. Reprod. (1998) [Pubmed]
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