Characterization of pigment epithelium‐derived factor receptor (PEDF‐R) using bioinformatics tools

PEDF is an extracellular multifunctional protein with demonstrable neurotrophic, antiangiogenic and antitumorigenic properties, and affinity for collagens and cell‐surface receptors. Using bioinformatic tools we examined the sequence of a novel gene from human retinal pigment epithelium (PEDF‐R) to reveal a role as PEDF receptor. ENSEMBLE searches showed that the PEDF‐R maps to locus 11p15.5 on human chromosome 11. BLASTn searches revealed putative PEDF‐R homologues in other species. PEDF‐R sequence fragments were found from various human organs, and RT‐PCR confirmed expression. The PEDF‐R sequence revealed 2.1kb transcripts coding for a 504‐residue polypeptide with four N‐glycosylation sites. Hydrophobicity plots anticipated 4 transmembrane domains with 3 intracellular and 2 extracellular loops. Northerns confirmed size of transcripts. Westerns revealed a PEDF‐R protein (81‐kDa) in eukaryotic membranes and cytosol. Immunohistochemistry with specific anti‐peptides confirmed transmembrane topology. BLASTp searches identified relatedness with members of the PNLP2 family, which exhibit lipase activities. A center PEDF‐R region with homology to collagen I interacted with PEDF. Bioinformatics revealed PEDF‐R as a lipase‐linked membrane protein with affinity for PEDF, suggesting a molecular pathway by which ligand/receptor interaction on the cell‐surface could generate a cellular signal.