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Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein

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The 39-40-kDa receptor-associated protein (RAP) binds to the members of the low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone. Using RAP affinity chromatography, we have purified a novel approximately 250-kDa brain protein and isolated the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine-based internalization signal and a large external part containing (from the N-terminal): 1) a segment homologous to domains in the yeast vacuolar protein sorting 10 protein, Vps10p, that binds carboxypeptidase Y, 2) five tandemly arranged YWTD repeats and a cluster of 11 class A repeats characteristic of the low density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor. Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis but not in several major organs. Both RAP and an antibody against a synthetic peptide derived from a sequence determined in the mature protein detected sorLA-1 in crude human brain extracts. The domain structure suggests that sorLA-1 is an endocytic receptor possibly implicated in the uptake of lipoproteins and of proteases.
Original languageEnglish
JournalJournal of Biological Chemistry
Pages (from-to)31379-31383
Number of pages5
Publication statusPublished - 6 Dec 1996

    Research areas

  • Amino Acid Sequence, Animals, Blotting, Northern, Caenorhabditis elegans, Carrier Proteins, Chromosome Mapping, DNA, Complementary, Electrophoresis, Polyacrylamide Gel, Glycoproteins, Heymann Nephritis Antigenic Complex, Humans, LDL-Receptor Related Protein-Associated Protein, LDL-Receptor Related Proteins, Membrane Glycoproteins, Membrane Transport Proteins, Molecular Chaperones, Molecular Sequence Data, Rats, Receptors, Cell Surface, Receptors, LDL, Tissue Distribution

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