Deletion of the amino-terminal domain of asialoglycoprotein receptor H1 allows cleavage of the internal signal sequence.
Human asialoglycoprotein receptor H1 is a single-spanning membrane protein with an amino-terminal domain of 40 residues exposed to the cytoplasm and the carboxyl-terminal domain translocated to the exoplasmic side of the membrane. It has been shown earlier that the transmembrane segment functions as an internal uncleaved signal sequence for insertion into the endoplasmic reticulum. In a deletion protein lacking almost the entire cytoplasmic domain, the signal sequence is cleaved at the carboxyl-terminal end of the transmembrane segment. All available criteria suggest that the protein is processed by signal peptidase. The cytoplasmic domain of the receptor does not directly inhibit signal cleavage since it does not detectably hinder cleavage of the normally amino-terminal signal sequence of influenza hemagglutinin in fusion proteins. We suggest that by its size or structure it affects the position of the receptor in the membrane and thus the accessibility of the potential cleavage site to signal peptidase.
D000595:Amino Acid Sequence; D000818:Animals; D037263:Asialoglycoprotein Receptor; D002872:Chromosome Deletion; D010450:Endopeptidases / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011817:Rabbits; D011971:Receptors, Immunologic / Q000032:analysis*; D012697:Serine Endopeptidases
D037263:Asialoglycoprotein Receptor; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D006596:Hexosaminidases; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase