| 释义 |
- Function
- Clinical significance
- Interactions
- References
- Further reading
- External links
{{Infobox_gene}}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: - DAB2,[8]
- DLG4,[9][9]
- GIPC1,[9][12][13]
- ITGB1BP1,[9]
- LDL-receptor-related protein associated protein,[10][11]
- LDLRAP1,[12]
- MAGI1,[13]
- MAPK8IP1,[9][13]
- MAPK8IP2,[14][15]
- NOS1AP,[14] and
- SYNJ2BP.[14]
{{Clear}} References 1. ^{{cite web | title = Entrez Gene: LRP2 low density lipoprotein-related protein 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4036| accessdate = }}
2. ^{{cite journal | vauthors = Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS | title = Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1) | journal = Genomics | volume = 22 | issue = 1 | pages = 88–93 | date = July 1994 | pmid = 7959795 | doi = 10.1006/geno.1994.1348 | url = }}
3. ^{{cite journal | vauthors = Farquhar MG | title = The unfolding story of megalin (gp330): now recognized as a drug receptor | journal = J. Clin. Invest. | volume = 96 | issue = 3 | pages = 1184 | date = September 1995 | pmid = 7657789 | pmc = 185736 | doi = 10.1172/JCI118149 | url = }}
4. ^{{cite journal|vauthors=Farquhar MG, Saito A, Kerjaschki D, Orlando RA|date=July 1995|title=The Heymann nephritis antigenic complex: megalin (gp330) and RAP|url=http://jasn.asnjournals.org/cgi/content/abstract/6/1/35|journal=J. Am. Soc. Nephrol.|volume=6|issue=1|pages=35–47|doi=|pmid=7579068|via=}}
5. ^{{cite journal|last1=Blazquez-Medela|first1=AM|last2=Garcia-Sanchez|first2=O|last3=Blanco-Gozalo|first3=V|last4=Quiros|first4=Y|last5=Montero|first5=MJ|last6=Martinez-Salgado|first6=C|last7=Lopez-Novoa|first7=JM|last8=Lopez-Hernandez|first8=FJ|title=Hypertension and Hyperglycemia Synergize to Cause Incipient Renal Tubular Alterations Resulting in Increased NGAL Urinary Excretion in Rats|journal=PLoS ONE|date=2016|volume=9|issue=8|page=e105988|doi=10.1371/journal.pone.0105988|pmid=25148248|pmc=4141836}}
6. ^{{cite journal | vauthors = Zheng G, Marino' M, Zhao J, McCluskey RT | title = Megalin (gp330): a putative endocytic receptor for thyroglobulin (Tg) | journal = Endocrinology | volume = 139 | issue = 3 | pages = 1462–5 | date = March 1998 | pmid = 9492085 | doi = 10.1210/en.139.3.1462 | url = http://endo.endojournals.org/cgi/content/full/139/3/1462 }}
7. ^{{cite journal | vauthors = 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 | title = Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes | journal = Nat. Genet. | volume = 39 | issue = 8 | pages = 957–9 | date = August 2007 | pmid = 17632512 | pmc = 2891728 | doi = 10.1038/ng2063 }}
8. ^{{cite journal | vauthors = Oleinikov AV, Zhao J, Makker SP | title = Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin | journal = Biochem. J. | volume = 347 | issue = 3| pages = 613–21 | date = May 2000 | pmid = 10769163 | pmc = 1220996 | doi = 10.1042/0264-6021:3470613}}
9. ^{{cite journal | vauthors = Larsson M, Hjälm G, Sakwe AM, Engström A, Höglund AS, Larsson E, Robinson RC, Sundberg C, Rask L | title = Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins | journal = Biochem. J. | volume = 373 | issue = Pt 2 | pages = 381–91 | date = July 2003 | pmid = 12713445 | pmc = 1223512 | doi = 10.1042/BJ20021958 }}
10. ^1 {{cite journal | vauthors = Lou X, McQuistan T, Orlando RA, Farquhar MG | title = GAIP, GIPC and Galphai3 are concentrated in endocytic compartments of proximal tubule cells: putative role in regulating megalin's function | journal = J. Am. Soc. Nephrol. | volume = 13 | issue = 4 | pages = 918–27 | date = April 2002 | pmid = 11912251 | doi = }}
11. ^{{cite journal | vauthors = Orlando RA, Farquhar MG | title = Functional domains of the receptor-associated protein (RAP) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 8 | pages = 3161–5 | date = April 1994 | pmid = 7512726 | pmc = 43535 | doi = 10.1073/pnas.91.8.3161}}
12. ^{{cite journal | vauthors = Nagai M, Meerloo T, Takeda T, Farquhar MG | title = The adaptor protein ARH escorts megalin to and through endosomes | journal = Mol. Biol. Cell | volume = 14 | issue = 12 | pages = 4984–96 | date = December 2003 | pmid = 14528014 | pmc = 284800 | doi = 10.1091/mbc.E03-06-0385 }}
13. ^{{cite journal | vauthors = Patrie KM, Drescher AJ, Goyal M, Wiggins RC, Margolis B | title = The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes | journal = J. Am. Soc. Nephrol. | volume = 12 | issue = 4 | pages = 667–77 | date = April 2001 | pmid = 11274227 | doi = }}
14. ^1 2 3 4 5 6 {{cite journal | vauthors = Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J | title = 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 | journal = J. Biol. Chem. | volume = 275 | issue = 33 | pages = 25616–24 | date = August 2000 | pmid = 10827173 | doi = 10.1074/jbc.M000955200 }}
15. ^1 2 {{cite journal | vauthors = Petersen HH, Hilpert J, Militz D, Zandler V, Jacobsen C, Roebroek AJ, Willnow TE | title = Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule | journal = J. Cell Sci. | volume = 116 | issue = Pt 3 | pages = 453–61 | date = February 2003 | pmid = 12508107 | doi = 10.1242/jcs.00243}}
Further reading {{refbegin | 2}}- {{cite journal | vauthors = Farquhar MG, Saito A, Kerjaschki D, Orlando RA | title = The Heymann nephritis antigenic complex: megalin (gp330) and RAP | journal = J. Am. Soc. Nephrol. | volume = 6 | issue = 1 | pages = 35–47 | year = 1995 | pmid = 7579068 | doi = }}
- {{cite journal | vauthors = Farquhar MG | title = The unfolding story of megalin (gp330): now recognized as a drug receptor | journal = J. Clin. Invest. | volume = 96 | issue = 3 | pages = 1184 | year = 1995 | pmid = 7657789 | pmc = 185736 | doi = 10.1172/JCI118149 }}
- {{cite journal | vauthors = Christensen EI, Birn H | title = Megalin and cubilin: multifunctional endocytic receptors | journal = Nat. Rev. Mol. Cell Biol. | volume = 3 | issue = 4 | pages = 256–66 | year = 2002 | pmid = 11994745 | doi = 10.1038/nrm778 }}
- {{cite journal | vauthors = 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 | title = Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis | journal = Nephrology (Carlton, Vic.) | volume = 10 Suppl | issue = | pages = S26–31 | year = 2006 | pmid = 16174284 | doi = 10.1111/j.1440-1797.2005.00453.x }}
- {{cite journal | vauthors = Fisher CE, Howie SE | title = The role of megalin (LRP-2/Gp330) during development | journal = Dev. Biol. | volume = 296 | issue = 2 | pages = 279–97 | year = 2006 | pmid = 16828734 | doi = 10.1016/j.ydbio.2006.06.007 }}
- {{cite journal | vauthors = Christensen EI, Gliemann J, Moestrup SK | title = Renal tubule gp330 is a calcium binding receptor for endocytic uptake of protein | journal = J. Histochem. Cytochem. | volume = 40 | issue = 10 | pages = 1481–90 | year = 1992 | pmid = 1382088 | doi = 10.1177/40.10.1382088 }}
- {{cite journal | vauthors = Raychowdhury R, Niles JL, McCluskey RT, Smith JA | title = Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor | journal = Science | volume = 244 | issue = 4909 | pages = 1163–5 | year = 1989 | pmid = 2786251 | doi = 10.1126/science.2786251 }}
- {{cite journal | vauthors = Orlando RA, Farquhar MG | title = Functional domains of the receptor-associated protein (RAP) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 8 | pages = 3161–5 | year = 1994 | pmid = 7512726 | pmc = 43535 | doi = 10.1073/pnas.91.8.3161 }}
- {{cite journal | vauthors = Kounnas MZ, Chappell DA, Strickland DK, Argraves WS | title = Glycoprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro | journal = J. Biol. Chem. | volume = 268 | issue = 19 | pages = 14176–81 | year = 1993 | pmid = 7686151 | doi = }}
- {{cite journal | vauthors = Kounnas MZ, Loukinova EB, Stefansson S, Harmony JA, Brewer BH, Strickland DK, Argraves WS | title = Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin | journal = J. Biol. Chem. | volume = 270 | issue = 22 | pages = 13070–5 | year = 1995 | pmid = 7768901 | doi = 10.1074/jbc.270.22.13070 }}
- {{cite journal | vauthors = Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS | title = Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1) | journal = Genomics | volume = 22 | issue = 1 | pages = 88–93 | year = 1994 | pmid = 7959795 | doi = 10.1006/geno.1994.1348 }}
- {{cite journal | vauthors = Lundgren S, Hjälm G, Hellman P, Ek B, Juhlin C, Rastad J, Klareskog L, Akerström G, Rask L | title = A protein involved in calcium sensing of the human parathyroid and placental cytotrophoblast cells belongs to the LDL-receptor protein superfamily | journal = Exp. Cell Res. | volume = 212 | issue = 2 | pages = 344–50 | year = 1994 | pmid = 8187828 | doi = 10.1006/excr.1994.1153 }}
- {{cite journal | vauthors = Moestrup SK, Nielsen S, Andreasen P, Jørgensen KE, Nykjaer A, Røigaard H, Gliemann J, Christensen EI | title = Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator-plasminogen activator inhibitor type-1 complexes | journal = J. Biol. Chem. | volume = 268 | issue = 22 | pages = 16564–70 | year = 1993 | pmid = 8344937 | doi = }}
- {{cite journal | vauthors = 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 | title = Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties | journal = Eur. J. Biochem. | volume = 239 | issue = 1 | pages = 132–7 | year = 1996 | pmid = 8706697 | doi = 10.1111/j.1432-1033.1996.0132u.x }}
- {{cite journal | vauthors = Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK, Herz J | title = Defective forebrain development in mice lacking gp330/megalin | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 16 | pages = 8460–4 | year = 1996 | pmid = 8710893 | pmc = 38693 | doi = 10.1073/pnas.93.16.8460 }}
- {{cite journal | vauthors = Cui S, Verroust PJ, Moestrup SK, Christensen EI | title = Megalin/gp330 mediates uptake of albumin in renal proximal tubule | journal = Am. J. Physiol. | volume = 271 | issue = 4 Pt 2 | pages = F900–7 | year = 1996 | pmid = 8898021 | doi = 10.1152/ajprenal.1996.271.4.F900}}
- {{cite journal | vauthors = Lundgren S, Carling T, Hjälm G, Juhlin C, Rastad J, Pihlgren U, Rask L, Akerström G, Hellman P | title = Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein | journal = J. Histochem. Cytochem. | volume = 45 | issue = 3 | pages = 383–92 | year = 1997 | pmid = 9071320 | doi = 10.1177/002215549704500306 }}
- {{cite journal | vauthors = Birn H, Verroust PJ, Nexo E, Hager H, Jacobsen C, Christensen EI, Moestrup SK | title = Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein | journal = J. Biol. Chem. | volume = 272 | issue = 42 | pages = 26497–504 | year = 1997 | pmid = 9334227 | doi = 10.1074/jbc.272.42.26497 }}
{{refend}} External links - [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=donnai GeneReviews/NCBI/NIH/UW entry on Donnai-Barrow Syndrome]
{{Lipoprotein metabolism}} |