Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor.
The nucleotide sequence of a partial cDNA for the bovine low-density lipoprotein (LDL) receptor revealed an open reading frame of 264 amino acids that encodes the COOH-terminal 25% of the receptor protein. The sequence predicts a cytoplasmic domain of 50 amino acids at the COOH terminus, followed in order by a membrane-spanning region of 27 hydrophobic amino acids and an externally disposed stretch of 42 amino acids, that is rich in serine and threonine residues and appears to be the site of O-linked glycosylation. This orientation was confirmed by proteolysis experiments in which the relevant fragments were localized by blotting with anti-peptide antibodies and a galactose-specific lectin. The extracytoplasmic domain of the LDL receptor contains a region that is 38% identical with a 96 amino acid sequence in the precursor to mouse epidermal growth factor (EGF), a peptide hormone. This unexpected homology raises the possibility that proteins involved in growth stimulation (e.g., EGF precursor) and nutrient delivery (e.g., LDL receptor) may have a common evolutionary origin.
D000302:Adrenal Cortex / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D004815:Epidermal Growth Factor / Q000235:genetics*; D005796:Genes; D008077:Lipoproteins, LDL / Q000378:metabolism; D010957:Plasmids; D011498:Protein Precursors / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D011973:Receptors, LDL
D008077:Lipoproteins, LDL; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D004815:Epidermal Growth Factor; D004247:DNA