LRP2

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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Low density lipoprotein-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.[1][2][3]

Function

LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman nephritis) and originally named gp330 and subsequently megalin[4] and later LRP2. LRP2/megalin is a multiligand binding receptor found in the plasma membrane of many absorptive epithelial cells. LRP2/megalin is a member of a family of receptors with structural similarities to the low density lipoprotein receptor (LDLR). LRP2/megalin functions to mediate endocytosis of ligands leading to degradation in lysosomes or transcytosis. LRP2/megalin can also form complexes with cubilin: those complexes are able to reabsorb several molecules and can be inhibited by sodium maleate.[5] LRP2 is expressed in epithelial cells of the thyroid (thyrocytes), where it can serve as a receptor for the protein thyroglobulin (Tg).[6]

Clinical significance

Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.[7]

Interactions

LRP2 has been shown to interact with:

References

  1. "Entrez Gene: LRP2 low density lipoprotein-related protein 2".
  2. Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS (July 1994). "Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1)". Genomics. 22 (1): 88–93. doi:10.1006/geno.1994.1348. PMID 7959795.
  3. Farquhar MG (September 1995). "The unfolding story of megalin (gp330): now recognized as a drug receptor". J. Clin. Invest. 96 (3): 1184. doi:10.1172/JCI118149. PMC 185736. PMID 7657789.
  4. Farquhar MG, Saito A, Kerjaschki D, Orlando RA (July 1995). "The Heymann nephritis antigenic complex: megalin (gp330) and RAP". J. Am. Soc. Nephrol. 6 (1): 35–47. PMID 7579068.
  5. Blazquez-Medela, AM; Garcia-Sanchez, O; Blanco-Gozalo, V; Quiros, Y; Montero, MJ; Martinez-Salgado, C; Lopez-Novoa, JM; Lopez-Hernandez, FJ (2016). "Hypertension and Hyperglycemia Synergize to Cause Incipient Renal Tubular Alterations Resulting in Increased NGAL Urinary Excretion in Rats". PLoS ONE. 9 (8): e105988. doi:10.1371/journal.pone.0105988. PMC 4141836. PMID 25148248.
  6. Zheng G, Marino' M, Zhao J, McCluskey RT (March 1998). "Megalin (gp330): a putative endocytic receptor for thyroglobulin (Tg)". Endocrinology. 139 (3): 1462–5. doi:10.1210/en.139.3.1462. PMID 9492085.
  7. Kantarci S, Al-Gazali L, Hill RS, Donnai D, Black GC, Bieth E, Chassaing N, Lacombe D, Devriendt K, Teebi A, Loscertales M, Robson C, Liu T, MacLaughlin DT, Noonan KM, Russell MK, Walsh CA, Donahoe PK, Pober BR (August 2007). "Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes". Nat. Genet. 39 (8): 957–9. doi:10.1038/ng2063. PMC 2891728. PMID 17632512.
  8. Oleinikov AV, Zhao J, Makker SP (May 2000). "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin". Biochem. J. 347 (3): 613–21. doi:10.1042/0264-6021:3470613. PMC 1220996. PMID 10769163.
  9. 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (August 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 (33): 25616–24. doi:10.1074/jbc.M000955200. PMID 10827173.
  10. Larsson M, Hjälm G, Sakwe AM, Engström A, Höglund AS, Larsson E, Robinson RC, Sundberg C, Rask L (July 2003). "Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins". Biochem. J. 373 (Pt 2): 381–91. doi:10.1042/BJ20021958. PMC 1223512. PMID 12713445.
  11. 11.0 11.1 Lou X, McQuistan T, Orlando RA, Farquhar MG (April 2002). "GAIP, GIPC and Galphai3 are concentrated in endocytic compartments of proximal tubule cells: putative role in regulating megalin's function". J. Am. Soc. Nephrol. 13 (4): 918–27. PMID 11912251.
  12. 12.0 12.1 12.2 Petersen HH, Hilpert J, Militz D, Zandler V, Jacobsen C, Roebroek AJ, Willnow TE (February 2003). "Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule". J. Cell Sci. 116 (Pt 3): 453–61. doi:10.1242/jcs.00243. PMID 12508107.
  13. Orlando RA, Farquhar MG (April 1994). "Functional domains of the receptor-associated protein (RAP)". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3161–5. doi:10.1073/pnas.91.8.3161. PMC 43535. PMID 7512726.
  14. Nagai M, Meerloo T, Takeda T, Farquhar MG (December 2003). "The adaptor protein ARH escorts megalin to and through endosomes". Mol. Biol. Cell. 14 (12): 4984–96. doi:10.1091/mbc.E03-06-0385. PMC 284800. PMID 14528014.
  15. Patrie KM, Drescher AJ, Goyal M, Wiggins RC, Margolis B (April 2001). "The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes". J. Am. Soc. Nephrol. 12 (4): 667–77. PMID 11274227.

Further reading

  • Farquhar MG, Saito A, Kerjaschki D, Orlando RA (1995). "The Heymann nephritis antigenic complex: megalin (gp330) and RAP". J. Am. Soc. Nephrol. 6 (1): 35–47. PMID 7579068.
  • Farquhar MG (1995). "The unfolding story of megalin (gp330): now recognized as a drug receptor". J. Clin. Invest. 96 (3): 1184. doi:10.1172/JCI118149. PMC 185736. PMID 7657789.
  • Christensen EI, Birn H (2002). "Megalin and cubilin: multifunctional endocytic receptors". Nat. Rev. Mol. Cell Biol. 3 (4): 256–66. doi:10.1038/nrm778. PMID 11994745.
  • Saito A, Takeda T, Hama H, Oyama Y, Hosaka K, Tanuma A, Kaseda R, Ueno M, Nishi S, Ogasawara S, Gondaira F, Suzuki Y, Gejyo F (2006). "Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis". Nephrology (Carlton, Vic.). 10 Suppl: S26–31. doi:10.1111/j.1440-1797.2005.00453.x. PMID 16174284.
  • Fisher CE, Howie SE (2006). "The role of megalin (LRP-2/Gp330) during development". Dev. Biol. 296 (2): 279–97. doi:10.1016/j.ydbio.2006.06.007. PMID 16828734.
  • Christensen EI, Gliemann J, Moestrup SK (1992). "Renal tubule gp330 is a calcium binding receptor for endocytic uptake of protein". J. Histochem. Cytochem. 40 (10): 1481–90. doi:10.1177/40.10.1382088. PMID 1382088.
  • Raychowdhury R, Niles JL, McCluskey RT, Smith JA (1989). "Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor". Science. 244 (4909): 1163–5. doi:10.1126/science.2786251. PMID 2786251.
  • Orlando RA, Farquhar MG (1994). "Functional domains of the receptor-associated protein (RAP)". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3161–5. doi:10.1073/pnas.91.8.3161. PMC 43535. PMID 7512726.
  • Kounnas MZ, Chappell DA, Strickland DK, Argraves WS (1993). "Glycoprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro". J. Biol. Chem. 268 (19): 14176–81. PMID 7686151.
  • Kounnas MZ, Loukinova EB, Stefansson S, Harmony JA, Brewer BH, Strickland DK, Argraves WS (1995). "Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin". J. Biol. Chem. 270 (22): 13070–5. doi:10.1074/jbc.270.22.13070. PMID 7768901.
  • Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS (1994). "Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1)". Genomics. 22 (1): 88–93. doi:10.1006/geno.1994.1348. PMID 7959795.
  • Lundgren S, Hjälm G, Hellman P, Ek B, Juhlin C, Rastad J, Klareskog L, Akerström G, Rask L (1994). "A protein involved in calcium sensing of the human parathyroid and placental cytotrophoblast cells belongs to the LDL-receptor protein superfamily". Exp. Cell Res. 212 (2): 344–50. doi:10.1006/excr.1994.1153. PMID 8187828.
  • Moestrup SK, Nielsen S, Andreasen P, Jørgensen KE, Nykjaer A, Røigaard H, Gliemann J, Christensen EI (1993). "Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator-plasminogen activator inhibitor type-1 complexes". J. Biol. Chem. 268 (22): 16564–70. PMID 8344937.
  • Hjälm G, Murray E, Crumley G, Harazim W, Lundgren S, Onyango I, Ek B, Larsson M, Juhlin C, Hellman P, Davis H, Akerström G, Rask L, Morse B (1996). "Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties". Eur. J. Biochem. 239 (1): 132–7. doi:10.1111/j.1432-1033.1996.0132u.x. PMID 8706697.
  • Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK, Herz J (1996). "Defective forebrain development in mice lacking gp330/megalin". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8460–4. doi:10.1073/pnas.93.16.8460. PMC 38693. PMID 8710893.
  • Cui S, Verroust PJ, Moestrup SK, Christensen EI (1996). "Megalin/gp330 mediates uptake of albumin in renal proximal tubule". Am. J. Physiol. 271 (4 Pt 2): F900–7. PMID 8898021.
  • Lundgren S, Carling T, Hjälm G, Juhlin C, Rastad J, Pihlgren U, Rask L, Akerström G, Hellman P (1997). "Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein". J. Histochem. Cytochem. 45 (3): 383–92. doi:10.1177/002215549704500306. PMID 9071320.
  • Birn H, Verroust PJ, Nexo E, Hager H, Jacobsen C, Christensen EI, Moestrup SK (1997). "Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein". J. Biol. Chem. 272 (42): 26497–504. doi:10.1074/jbc.272.42.26497. PMID 9334227.

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