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Lrp2

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Title: Lrp2  
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Subject: Donnai–Barrow syndrome, Lipoprotein receptor-related protein, APOA5, LRP10, LRP1B
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Lrp2

Low density lipoprotein receptor-related protein 2
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; DBS; GP330
External IDs ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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]

Contents

  • Function 1
  • Clinical significance 2
  • Interactions 3
  • References 4
  • Further reading 5
  • External links 6

Function

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

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

Interactions

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

  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.  
  3. ^ Farquhar MG (September 1995). "The unfolding story of megalin (gp330): now recognized as a drug receptor". J. Clin. Invest. 96 (3): 1184.  
  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.  
  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.  
  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.  
  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.  
  8. ^ Orlando, R A; Farquhar M G (April 1994). "Functional domains of the receptor-associated protein (RAP)".  
  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.  
  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.  
  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.  
  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.  
  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.  
  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.  

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.  
  • Farquhar MG (1995). "The unfolding story of megalin (gp330): now recognized as a drug receptor". J. Clin. Invest. 96 (3): 1184.  
  • Christensen EI, Birn H (2002). "Megalin and cubilin: multifunctional endocytic receptors". Nat. Rev. Mol. Cell Biol. 3 (4): 256–66.  
  • 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.  
  • Fisher CE, Howie SE (2006). "The role of megalin (LRP-2/Gp330) during development". Dev. Biol. 296 (2): 279–97.  
  • 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.  
  • 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.  
  • Orlando RA, Farquhar MG (1994). "Functional domains of the receptor-associated protein (RAP)". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3161–5.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  

External links

  • GeneReviews/NCBI/NIH/UW entry on Donnai-Barrow Syndrome


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