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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/15 15:48:16」(JST)

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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:

DAB2,^[7]
DLG4,^[8]^[9]
GIPC1,^[8]^[10]^[11]
ITGB1BP1,^[8]
LDL-receptor-related protein associated protein,^[10]^[12]
LDLRAP1,^[13]
MAGI1,^[14]
MAPK8IP1,^[8]^[11]
MAPK8IP2,^[8]^[11]
NOS1AP,^[8] and
SYNJ2BP.^[8]

References

^ "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.
^ ^a ^b ^c ^d ^e ^f ^g 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.
^ ^a ^b 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.
^ ^a ^b ^c 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

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. アミノグリコシドの腎毒性および聴覚毒性の病因および予防 pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity
2. ビタミンB12および葉酸欠乏症の生理学 physiology of vitamin b12 and folate deficiency
3. 膜性腎症の原因および診断 causes and diagnosis of membranous nephropathy
4. ビタミンD欠乏症の原因および抵抗性 causes of vitamin d deficiency and resistance
5. ハーブ含有アリストロキン酸（AA）誘発性腎症 nephropathy induced by aristolochic acid aa containing herbs

English Journal

Deficiency of Angiotensinogen in Hepatocytes Markedly Decreases Blood Pressure in Lean and Obese Male Mice.

Yiannikouris F1, Wang Y1, Shoemaker R1, Larian N1, Thompson J1, English VL1, Charnigo R1, Su W1, Gong M1, Cassis LA2.
Hypertension.Hypertension.2015 Oct;66(4):836-42. doi: 10.1161/HYPERTENSIONAHA.115.06040. Epub 2015 Aug 24.
We recently demonstrated that adipocyte deficiency of angiotensinogen (AGT) ablated high-fat diet-induced elevations in plasma angiotensin II (Ang II) concentrations and obesity-hypertension in male mice. Hepatocytes are the predominant source of systemic AGT. Therefore, in this study, we defined th
PMID 26303292

Elevation of urinary methylmolonic acid induces the suppression of megalin-mediated endocytotic cycles during vitamin B12 deficiency.

Shiga T1, Kawata T2, Furusho T3, Tadokoro T1, Suzuki T1, Yamamoto Y1.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2015 Sep 18;465(2):206-12. doi: 10.1016/j.bbrc.2015.07.151. Epub 2015 Aug 4.
Megalin is a scavenger receptor that serves in the endocytosis of a highly diverse group of ligands that includes Vitamin B12. We found an accumulation of megalin closed to apical region in renal proximal tubule cells of Vitamin B12-deficient rats. Interestingly, Vitamin B12 levels also controlled r
PMID 26248135

Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway.

Kawano H1, Ito Y2, Kanai F3, Nakamura E3, Tada N3, Takai S4, Horie S1, Kobayashi T2, Hino O2.
Oncology reports.Oncol Rep.2015 Sep 8. doi: 10.3892/or.2015.4254. [Epub ahead of print]
The model animal of renal cell carcinoma (RCC), the Eker rat, has a germline mutation in the tuberous sclerosis 2 (Tsc2) gene. Heterozygous mutants develop RCCs by second hit in the wild-type Tsc2 allele, whereas homozygous mutants are embryonic lethal. In the present study, a new cell differentiat
PMID 26352760

Japanese Journal

腎症・脂質代謝異常と糖質調整 (特集ガイドラインに基づく糖質調整とその実際)

内分泌・糖尿病・代謝内科 = Endocrinology, diabetology & metabolism 42(2), 104-107, 2016-02
NAID 40020751533

尿蛋白の分析からわかる事―近位尿細管における蛋白の陽性荷電嗜好性再吸収機構―

日本小児腎臓病学会雑誌 28(1), 1-5, 2015
NAID 130005102911

生体腎移植後に発生した移植腎内リンパ嚢胞に対し，腹腔鏡下腎嚢胞開窓術を施行した1例

日本泌尿器科學會雑誌 105(3), 139-143, 2014
NAID 130005093153

Related Pictures

Physiology of Thyroid Gland - ppt video online download New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Megalin and cubilin in proximal tubule protein reabsorption: from experimental models Megalin and the neurodevelopmental biology of sonic hedgehog and retinol | Journal of Megalin and cubilin: multifunctional endocytic receptors | Nature Reviews Molecular Megalin and its associated molecules involved in receptor-mediated | Download ARH directs megalin to the endocytic recycling compartment to regulate its proteolysis Anti-Lrp2 / Megalin antibody [CD7D5] (ab184676) | Abcam

★リンクテーブル★

リンク元	「LDL-receptor related protein 2」「メガリン」

「LDL-receptor related protein 2」

LRP2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2M0P
Identifiers
Aliases	LRP2, DBS, GP330, LDL receptor related protein 2
External IDs	MGI: 95794 HomoloGene: 20952 GeneCards: 4036
Genetically Related Diseases
Disease Name	References
	[1]
Targeted by Drug
Drug Name	References
Gene ontology
Molecular function	• calcium ion binding; • SH3 domain binding; • metal ion binding; • protein binding;
Cellular component	• integral component of membrane; • endosome; • Golgi apparatus; • membrane; • receptor complex; • plasma 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;
Biological process	• endocytosis; • ventricular septum development; • vitamin D metabolic process; • lipid metabolic process; • fat-soluble vitamin metabolic process; • receptor-mediated endocytosis; • coronary vasculature development; • retinoid metabolic process; • protein glycosylation; • aorta development; • heart development; • vitamin metabolic process; • small molecule metabolic process; • phototransduction, visible light; • forebrain development; • cell proliferation;
	Sources:Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	4036
	14725
	ENSG00000081479
	ENSMUSG00000027070
	P98164
	A2ARV4
	NM_004525
	NM_001081088
	NP_004516.2
	NP_001074557.1
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

LDL受容体関連タンパク質2、LDLレセプター関連タンパク質2

関: megalin

「メガリン」

　　[★]

英: megalin
関: LDL受容体関連タンパク質2

[entrez-1] "Entrez Gene: LRP2 low density lipoprotein-related protein 2".

[pmid7959795-2] 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.

[pmid7657789-3] 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.

[pmid7579068-4] 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.

[pmid9492085-5] 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.

[pmid17632512-6] 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.

[pmid10769163-7] 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.

[pmid10827173-8] ^ ^a ^b ^c ^d ^e ^f ^g 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.

[pmid12713445-9] 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.

[pmid11912251-10] 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.

[pmid12508107-11] 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.

[pmid7512726-12] 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.

[pmid14528014-13] 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.

[pmid11274227-14] 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.

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案内

megalin