LRP2

LRP2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2M0P
Identifiers
Aliases	LRP2, DBS, GP330, LDL receptor related protein 2, LRP-2
External IDs	OMIM: 600073 MGI: 95794 HomoloGene: 20952 GeneCards: LRP2
Gene location (Human)
Chr.	Chromosome 2 (human)[1]
End	169,362,534 bp[1]
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)[2]
End	69,586,065 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• calcium ion binding; • SH3 domain binding; • metal ion binding; • GO:0001948 protein binding; • low-density lipoprotein receptor activity; • drug binding; • steroid hormone receptor binding; • chaperone binding;
Cellular component	• integral component of membrane; • endosome; • Golgi apparatus; • membrane; • receptor complex; • cell membrane; • endocytic vesicle; • apical part of cell; • brush border membrane; • lysosomal membrane; • apical plasma membrane; • endoplasmic reticulum; • brush border; • clathrin-coated pit; • lysosome; • extracellular exosome; • clathrin-coated vesicle membrane; • external side of plasma membrane; • axon; • dendrite; • endosome lumen; • cell projection;
Biological process	• endocytosis; • ventricular septum development; • vitamin D metabolic process; • lipid metabolism; • receptor-mediated endocytosis; • coronary vasculature development; • retinoid metabolic process; • aorta development; • heart development; • forebrain development; • cellular proliferation; • vitamin metabolic process; • lipoprotein transport; • membrane organization; • neural tube closure; • secondary heart field specification; • outflow tract septum morphogenesis; • ventricular compact myocardium morphogenesis; • nervous system development; • sensory perception of sound; • male gonad development; • metal ion transport; • negative regulation of BMP signaling pathway; • positive regulation of neurogenesis; • vagina development; • coronary artery morphogenesis; • pulmonary artery morphogenesis; • positive regulation of oligodendrocyte progenitor proliferation; • neuron projection arborization; • folic acid import across plasma membrane; • positive regulation of lysosomal protein catabolic process;
	Sources:Amigo / QuickGO
Orthologs
	4036
	14725
	ENSG00000081479
	ENSMUSG00000027070
	P98164
	A2ARV4
	NM_004525
	NM_001081088
	NP_004516
	NP_001074557
	Wikidata
View/Edit Human	View/Edit Mouse

Low density lipoprotein-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.[5][6][7]

Function

LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman nephritis) and originally named gp330 and subsequently megalin[8] 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. LRP2 is expressed in epithelial cells of the thyroid (thyrocytes), where it can serve as a receptor for the protein thyroglobulin (Tg).[9]

Clinical significance

Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.[10]

Interactions

LRP2 has been shown to interact with:

DAB2,[11]
DLG4,[12][13]
GIPC1,[12][14][15]
ITGB1BP1,[12]
LDL-receptor-related protein associated protein,[14][16]
LDLRAP1,[17]
MAGI1,[18]
MAPK8IP1,[12][15]
MAPK8IP2,[12][15]
NOS1AP,[12] and
SYNJ2BP.[12]

References

GRCh38: Ensembl release 89: ENSG00000081479 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000027070 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: LRP2 low density lipoprotein-related protein 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

External links

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000081479 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027070 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: LRP2 low density lipoprotein-related protein 2".

[pmid7959795-6] 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.

[pmid7657789-7] 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.

[pmid7579068-8] 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.

[pmid9492085-9] 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.

[pmid17632512-10] 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.

[pmid10769163-11] 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.

[pmid10827173-12] 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.

[pmid12713445-13] 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.

[pmid11912251-14] 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.

[pmid12508107-15] 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.

[pmid7512726-16] 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.

[pmid14528014-17] 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.

[pmid11274227-18] 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.

Lipids: lipoprotein particle metabolism
Lipoprotein particle classes and subclasses	delivery of TGs: Chylomicron VLDL delivery of C and CE: IDL LDL lb LDL sd LDL Lp(a) HDL Remnant cholesterol
Apolipoproteins	APOA 1 2 4 5 APOB APOC 1 2 3 4 APOD APOE APOH SAA SAA1
Extracellular enzymes	LCAT LIPC LPL
Lipid transfer proteins	CETP MTTP PLTP
Cell surface receptors	HDL: SCARB1 IDL: LRP LRP1 LRP1B LRP2 LRP3 LRP4 LRP5 LRP5L LRP6 LRP8 LRP10 LRP11 LRP12 LDL: LDLR LRPAP1
ATP-binding cassette transporter	ABCA1 ABCG5 ABCG8