Low density lipoprotein receptor adapter protein 1

Low density lipoprotein receptor adaptor protein 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2G30
Identifiers
Symbols	LDLRAP1; ARH; ARH1; ARH2; FHCB1; FHCB2
External IDs	OMIM: 605747 MGI: 2140175 HomoloGene: 9219 GeneCards: LDLRAP1 Gene
Gene Ontology Molecular function • beta-amyloid binding • phosphotyrosine binding • protein binding • phosphatidylinositol-4,5-bisphosphate binding • receptor signaling complex scaffold activity • clathrin binding • signaling adaptor activity • AP-2 adaptor complex binding • clathrin adaptor activity • low-density lipoprotein particle receptor binding Cellular component • cytoplasm • early endosome • cytosol • neurofilament • internal side of plasma membrane • basal plasma membrane • AP-1 adaptor complex • AP-2 adaptor complex • axon • recycling endosome Biological process • transport • receptor-mediated endocytosis • steroid metabolic process • cholesterol metabolic process • positive regulation of signal transduction • receptor internalization • cholesterol homeostasis • amyloid precursor protein metabolic process • regulation of protein binding • positive regulation of receptor-mediated endocytosis • regulation of establishment of protein localization in plasma membrane • receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport • positive regulation of cholesterol metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	26119	100017
Ensembl	ENSG00000157978	ENSMUSG00000037295
UniProt	Q5SW96	Q8C142
RefSeq (mRNA)	NM_015627.2	NM_145554.2
RefSeq (protein)	NP_056442.2	NP_663529.2
Location (UCSC)	Chr 1: 25.87 – 25.9 Mb	Chr 4: 134.3 – 134.32 Mb
PubMed search	[1]	[2]

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

The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD 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 and LRP2.

Further reading

• Barbagallo CM, Emmanuele G, Cefalù AB, et al. (2003). "Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene.". Atherosclerosis 166 (2): 395–400. doi:10.1016/S0021-9150(02)00379-9. PMID 12535754. 
• Garcia CK, Wilund K, Arca M, et al. (2001). "Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.". Science 292 (5520): 1394–8. doi:10.1126/science.1060458. PMID 11326085. 
• Arca M, Zuliani G, Wilund K, et al. (2002). "Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis.". Lancet 359 (9309): 841–7. doi:10.1016/S0140-6736(02)07955-2. PMID 11897284. 
• Al-Kateb H, Bähring S, Hoffmann K, et al. (2002). "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. doi:10.1161/01.RES.0000018002.43041.08. PMID 12016260. 
• He G, Gupta S, Yi M, et al. (2003). "ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2.". J. Biol. Chem. 277 (46): 44044–9. doi:10.1074/jbc.M208539200. PMID 12221107. 
• Wilund KR, Yi M, Campagna F, et al. (2003). "Molecular mechanisms of autosomal recessive hypercholesterolemia.". Hum. Mol. Genet. 11 (24): 3019–30. doi:10.1093/hmg/11.24.3019. PMID 12417523. 
• Mishra SK, Watkins SC, Traub LM (2003). "The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery.". Proc. Natl. Acad. Sci. U.S.A. 99 (25): 16099–104. doi:10.1073/pnas.252630799. PMC 138571. PMID 12451172. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=138571. 
• Eden ER, Patel DD, Sun XM, et al. (2003). "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. doi:10.1172/JCI16445. PMC 151635. PMID 12464675. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151635. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Jones C, Hammer RE, Li WP, et al. (2003). "Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia.". J. Biol. Chem. 278 (31): 29024–30. doi:10.1074/jbc.M304855200. PMID 12746448. 
• Harada-Shiba M, Takagi A, Miyamoto Y, et al. (2003). "Clinical features and genetic analysis of autosomal recessive hypercholesterolemia.". J. Clin. Endocrinol. Metab. 88 (6): 2541–7. doi:10.1210/jc.2002-021487. PMID 12788851. 
• Nagai M, Meerloo T, Takeda T, Farquhar MG (2004). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=284800. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Michaely P, Li WP, Anderson RG, et al. (2004). "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. doi:10.1074/jbc.M405242200. PMID 15166224. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Canizales-Quinteros S, Aguilar-Salinas CA, Huertas-Vázquez A, et al. (2005). "A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.". Hum. Genet. 116 (1-2): 114–20. doi:10.1007/s00439-004-1192-9. PMID 15599766. 
• Mishra SK, Keyel PA, Edeling MA, et al. (2005). "Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein.". J. Biol. Chem. 280 (19): 19270–80. doi:10.1074/jbc.M501029200. PMID 15728179. 
• Sirinian MI, Belleudi F, Campagna F, et al. (2006). "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. doi:10.1074/jbc.M504343200. PMID 16129683. 
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.