LRP2

Low density lipoprotein receptor-related protein 2
Identifiers
Symbols	LRP2; DBS; GP330
External IDs	OMIM: 600073 MGI: 95794 HomoloGene: 20952 GeneCards: LRP2 Gene
Gene Ontology Molecular function • receptor activity • calcium ion binding • protein binding • SH3 domain binding • hemoglobin binding • lipoprotein transporter activity Cellular component • extracellular space • membrane fraction • cytoplasm • lysosome • endosome • endoplasmic reticulum • Golgi apparatus • plasma membrane • coated pit • integral to membrane • apical plasma membrane • endocytic vesicle • brush border membrane Biological process • protein glycosylation • lipid metabolic process • vitamin metabolic process • endocytosis • receptor-mediated endocytosis • aging • steroid metabolic process • cell proliferation • response to X-ray • endosome transport • hemoglobin import • forebrain development • organ regeneration • response to retinoic acid • response to vitamin D • vitamin D metabolic process • hormone biosynthetic process • response to drug • transcytosis • hormone secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4036	14725
Ensembl	ENSG00000081479	ENSMUSG00000027070
UniProt	P98164	n/a
RefSeq (mRNA)	NM_004525.2	NM_001081088.1
RefSeq (protein)	NP_004516.2	NP_001074557.1
Location (UCSC)	Chr 2: 169.98 – 170.22 Mb	Chr 2: 69.26 – 69.42 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

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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4036. 
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=185736. 
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. http://jasn.asnjournals.org/cgi/content/abstract/6/1/35. 
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. http://endo.endojournals.org/cgi/content/full/139/3/1462. 
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2891728. 
7. ^ ^{a b} Lou, Xiaojing; McQuistan Tammie, Orlando Robert A, Farquhar Marilyn Gist (Apr. 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 (Apr. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43535. 
9. ^ Nagai, Masaaki; Meerloo Timo, Takeda Tetsuro, Farquhar Marilyn Gist (Dec. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=284800. 
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 (Aug. 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 (Feb. 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 (Apr. 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 (Jul. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223512. 
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: 613–21. doi:10.1042/0264-6021:3470613. ISSN 0264-6021. PMC 1220996. PMID 10769163. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1220996. 

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=185736. 
• 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. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43535. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=38693. 
• 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. 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

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