Low-density lipoprotein receptor adapter protein 1 explained

Low-density lipoprotein receptor adapter protein 1 is a protein that in humans is encoded by the LDLRAP1 gene.^[1]

The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTB) domain. The PTB domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia.

Interactions

LDLRAP1 has been shown to interact with AP2B1^{[2] [3]} and LRP2.^[4]

Further reading

• Barbagallo CM, Emmanuele G, Cefalù AB, etal . Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene. . Atherosclerosis . 166 . 2 . 395–400 . 2003 . 12535754 . 10.1016/S0021-9150(02)00379-9 .
• Garcia CK, Wilund K, Arca M, etal . Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. . Science . 292 . 5520 . 1394–8 . 2001 . 11326085 . 10.1126/science.1060458 . 2001Sci...292.1394G . 18718435 . free .
• Arca M, Zuliani G, Wilund K, etal . Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis. . Lancet . 359 . 9309 . 841–7 . 2002 . 11897284 . 10.1016/S0140-6736(02)07955-2 . 10028777 .
• Al-Kateb H, Bähring S, Hoffmann K, etal . Mutation in the ARH gene and a chromosome 13q locus influence cholesterol levels in a new form of digenic-recessive familial hypercholesterolemia. . Circ. Res. . 90 . 9 . 951–8 . 2002 . 12016260 . 10.1161/01.RES.0000018002.43041.08 . 1154851 .
• He G, Gupta S, Yi M, etal . ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. . J. Biol. Chem. . 277 . 46 . 44044–9 . 2003 . 12221107 . 10.1074/jbc.M208539200 . free .
• Wilund KR, Yi M, Campagna F, etal . Molecular mechanisms of autosomal recessive hypercholesterolemia. . Hum. Mol. Genet. . 11 . 24 . 3019–30 . 2003 . 12417523 . 10.1093/hmg/11.24.3019 . free .
• Mishra SK, Watkins SC, Traub LM . The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 25 . 16099–104 . 2003 . 12451172 . 10.1073/pnas.252630799 . 138571 . 2002PNAS...9916099M . free .
• Eden ER, Patel DD, Sun XM, etal . Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1. . J. Clin. Invest. . 110 . 11 . 1695–702 . 2003 . 12464675 . 10.1172/JCI16445 . 151635 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Jones C, Hammer RE, Li WP, etal . Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia. . J. Biol. Chem. . 278 . 31 . 29024–30 . 2003 . 12746448 . 10.1074/jbc.M304855200 . free .
• Harada-Shiba M, Takagi A, Miyamoto Y, etal . Clinical features and genetic analysis of autosomal recessive hypercholesterolemia. . J. Clin. Endocrinol. Metab. . 88 . 6 . 2541–7 . 2003 . 12788851 . 10.1210/jc.2002-021487 . free .
• Nagai M, Meerloo T, Takeda T, Farquhar MG . The adaptor protein ARH escorts megalin to and through endosomes. . Mol. Biol. Cell . 14 . 12 . 4984–96 . 2004 . 14528014 . 10.1091/mbc.E03-06-0385 . 284800 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Michaely P, Li WP, Anderson RG, etal . The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits. . J. Biol. Chem. . 279 . 32 . 34023–31 . 2004 . 15166224 . 10.1074/jbc.M405242200 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Canizales-Quinteros S, Aguilar-Salinas CA, Huertas-Vázquez A, etal . A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia. . Hum. Genet. . 116 . 1–2 . 114–20 . 2005 . 15599766 . 10.1007/s00439-004-1192-9 . 19424659 .
• Mishra SK, Keyel PA, Edeling MA, etal . Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein. . J. Biol. Chem. . 280 . 19 . 19270–80 . 2005 . 15728179 . 10.1074/jbc.M501029200 . free .
• Sirinian MI, Belleudi F, Campagna F, etal . Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes. . J. Biol. Chem. . 280 . 46 . 38416–23 . 2006 . 16129683 . 10.1074/jbc.M504343200 . free . 11380/304538 . free .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .

Notes and References

1. Web site: Entrez Gene: LDLRAP1 low density lipoprotein receptor adaptor protein 1.
2. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Oct 2005 . Towards a proteome-scale map of the human protein-protein interaction network . . 437 . 7062 . 1173–8 . England. 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
3. He . Guocheng . Gupta Sarita . Yi Ming . Michaely Peter . Hobbs Helen H . Cohen Jonathan C . Nov 2002 . ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2 . J. Biol. Chem. . 277 . 46 . 44044–9 . United States. 0021-9258. 12221107 . 10.1074/jbc.M208539200 . free .
4. Nagai . Masaaki . Meerloo Timo . Takeda Tetsuro . Farquhar Marilyn Gist . Dec 2003 . The adaptor protein ARH escorts megalin to and through endosomes . Mol. Biol. Cell . 14 . 12 . 4984–96 . United States. 1059-1524. 14528014 . 10.1091/mbc.E03-06-0385 . 284800 .