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General Comment |
Jacobsen L, et al 1996 reported the molecular characterization of a novel human hybrid-type receptor
that binds the alpha2-macroglobulin receptor-associated protein.
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, the authors 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. 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.
NCBI Summary:
This gene encodes a protein that belongs to the families of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins, of low density lipoprotein receptor (LDLR) proteins, and of fibronectin type III repeats proteins. In addition to VPS10, LDLR and fibronectin type 3 domains, this protein also includes an epidermal growth factor precursor-like module, a single transmembrane segment and a cytoplasmic tail with features similar to endocytosis- and sorting-competent receptors. Members of the VPS10 domain-containing receptor family are large with many exons but the CDS lengths are usually less than 3700 nt; this gene is an exception to the pattern with a CDS length greater than 6600 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. The encoded protein is mainly intracellular and localizes in the paranuclear compartment. It is synthesized as a preproprotein, and when the propeptide is still attached, no binding occurs to the VPS10 domain. This gene is strongly expressed in the central nervous system.
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