Low-density lipoprotein receptor adapter protein 1

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

LDLRAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2G30
Identifiers
Aliases	LDLRAP1, ARH, ARH1, ARH2, FHCB1, FHCB2, low density lipoprotein receptor adaptor protein 1, FHCL4
External IDs	OMIM: 605747; MGI: 2140175; HomoloGene: 9219; GeneCards: LDLRAP1; OMA:LDLRAP1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p36.11 Start 25,543,606 bp End 25,568,886 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4|4 D3 Start 134,468,865 bp End 134,495,335 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar hemisphere right hemisphere of cerebellum C1 segment granulocyte spleen endothelial cell lymph node body of pancreas hair follicle islet of Langerhans Top expressed in otic vesicle saccule otic placode granulocyte molar lip lumbar subsegment of spinal cord tibiofemoral joint conjunctival fornix calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function AP-2 adaptor complex binding clathrin adaptor activity phosphotyrosine residue binding clathrin binding amyloid-beta binding signaling adaptor activity low-density lipoprotein particle receptor binding protein binding phosphatidylinositol-4,5-bisphosphate binding signaling receptor complex adaptor activity AP-1 adaptor complex binding Cellular component cytoplasm AP-1 adaptor complex recycling endosome cytosol basal plasma membrane cytoplasmic side of plasma membrane AP-2 adaptor complex neurofilament axon early endosome plasma membrane clathrin-coated vesicle membrane Biological process positive regulation of receptor-mediated endocytosis steroid metabolic process endocytosis receptor-mediated endocytosis involved in cholesterol transport lipid metabolism receptor internalization amyloid precursor protein metabolic process receptor-mediated endocytosis positive regulation of cholesterol metabolic process cholesterol homeostasis regulation of protein binding cholesterol metabolic process positive regulation of signal transduction low-density lipoprotein particle clearance membrane organization positive regulation of receptor-mediated endocytosis involved in cholesterol transport regulation of protein localization to plasma membrane cholesterol transport cellular response to cytokine stimulus positive regulation of vascular associated smooth muscle cell proliferation positive regulation of low-density lipoprotein particle clearance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26119 100017 Ensembl ENSG00000157978 ENSMUSG00000037295 UniProt Q5SW96 Q8C142 RefSeq (mRNA) NM_015627 NM_145554 RefSeq (protein) NP_056442 NP_663529 Location (UCSC) Chr 1: 25.54 – 25.57 Mb Chr 4: 134.47 – 134.5 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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 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. Bibcode:2001Sci...292.1394G. doi:10.1126/science.1060458. PMID 11326085. S2CID 18718435.
• 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. S2CID 10028777.
• 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. S2CID 1154851.
• 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. Bibcode:2002PNAS...9916099M. doi:10.1073/pnas.252630799. PMC 138571. PMID 12451172.
• 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.
• 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• 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.
• 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.
• 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. S2CID 19424659.
• 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. hdl:11380/304538. 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.