LRP2

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Low density lipoprotein receptor-related protein 2
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols LRP2 ; DBS; GP330
External IDs OMIM600073 MGI95794 HomoloGene20952 ChEMBL: 1255140 GeneCards: LRP2 Gene
RNA expression pattern
PBB GE LRP2 205710 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4036 14725
Ensembl ENSG00000081479 ENSMUSG00000027070
UniProt P98164 A2ARV4
RefSeq (mRNA) NM_004525 NM_001081088
RefSeq (protein) NP_004516 NP_001074557
Location (UCSC) Chr 2:
169.98 – 170.22 Mb
Chr 2:
69.42 – 69.59 Mb
PubMed search [1] [2]

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[edit]

LRP2 is a multiligand binding receptor found in the plasma membrane of many absorptive epithelial cells. LRP2 is a member of a family of receptors with structural similarities to the low density lipoprotein receptor (LDLR). LRP2 functions to mediate endocytosis of ligands leading to degradation in lysosomes or transcytosis. LRP2 (previously called glycoprotein 330) together with RAP (LRPAP1) forms the Heymann nephritis antigenic complex.[4] LRP2 is expressed in epithelial cells of the thyroid (thyrocytes), where it can serve as a receptor for the protein thyroglobulin (Tg).[5]

Clinical significance[edit]

Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.[6]

Interactions[edit]

LRP2 has been shown to interact with LDL-receptor-related protein associated protein,[7][8] LDLRAP1,[9] MAPK8IP2,[10][11] MAGI1,[12] SYNJ2BP,[10] DLG4,[10][13] NOS1AP,[10] DAB2,[14] ITGB1BP1,[10] MAPK8IP1[10][11] and GIPC1.[7][10][11]

References[edit]

  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. ^ 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. 
  6. ^ Kantarci S, Al-Gazali L, Hill RS, et al. (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. 
  7. ^ a b Lou, Xiaojing; McQuistan Tammie, Orlando Robert A, Farquhar Marilyn Gist (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. (United States) 13 (4): 918–27. ISSN 1046-6673. PMID 11912251. 
  8. ^ Orlando, R A; Farquhar M G (April 1994). "Functional domains of the receptor-associated protein (RAP)". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (8): 3161–5. doi:10.1073/pnas.91.8.3161. ISSN 0027-8424. PMC 43535. PMID 7512726. 
  9. ^ Nagai, Masaaki; Meerloo Timo, Takeda Tetsuro, Farquhar Marilyn Gist (December 2003). "The Adaptor Protein ARH Escorts Megalin to and through Endosomes". Mol. Biol. Cell (United States) 14 (12): 4984–96. doi:10.1091/mbc.E03-06-0385. ISSN 1059-1524. PMC 284800. PMID 14528014. 
  10. ^ a b c d e f g Gotthardt, M; Trommsdorff M, Nevitt M F, Shelton J, Richardson J A, 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. (UNITED STATES) 275 (33): 25616–24. doi:10.1074/jbc.M000955200. ISSN 0021-9258. PMID 10827173. 
  11. ^ a b c Petersen, Helle Heibroch; Hilpert Jan, Militz Daniel, Zandler Valerie, Jacobsen Christian, Roebroek Anton J M, Willnow Thomas E (February 2003). "Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule". J. Cell. Sci. (England) 116 (Pt 3): 453–61. doi:10.1242/jcs.00243. ISSN 0021-9533. PMID 12508107. 
  12. ^ Patrie, K M; Drescher A J, Goyal M, Wiggins R C, Margolis B (April 2001). "The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes". J. Am. Soc. Nephrol. (United States) 12 (4): 667–77. ISSN 1046-6673. PMID 11274227. 
  13. ^ Larsson, Mårten; Hjälm Göran, Sakwe Amos M, Engström Ake, Höglund Anna-Stina, Larsson Erik, Robinson Robert C, Sundberg Christian, Rask Lars (July 2003). "Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins". Biochem. J. (England) 373 (Pt 2): 381–91. doi:10.1042/BJ20021958. ISSN 0264-6021. PMC 1223512. PMID 12713445. 
  14. ^ Oleinikov, A V; Zhao J, Makker S P (May 2000). "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin". Biochem. J. (ENGLAND). 347 Pt 3 (3): 613–21. doi:10.1042/0264-6021:3470613. ISSN 0264-6021. PMC 1220996. PMID 10769163. 

Further reading[edit]

  • 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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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. 

External links[edit]