The membrane-spanning segment of invariant chain (I gamma) contains a potentially cleavable signal sequence.
The human invariant chain (I gamma) of class II histocompatibility antigens spans the membrane of the endoplasmic reticulum once. It exposes a small amino-terminal domain on the cytoplasmic side and a carboxy-terminal, glycosylated domain on the exoplasmic side of the membrane. When the exoplasmic domain of I gamma is replaced by the cytoplasmic protein chloramphenicol acetyltransferase (CAT), CAT becomes the exoplasmic, glycosylated domain of the resulting membrane protein I gamma CAT. Deletion of the hydrophilic cytoplasmic domain from I gamma CAT gives rise to a secreted protein from which an amino-terminal segment is cleaved, most likely by signal peptidase. We conclude that the membrane-spanning region of I gamma contains a signal sequence in its amino-terminal half and that hydrophilic residues at the amino-terminal end of a signal sequence can determine cleavage by signal peptidase.
D000123:Acetyltransferases / Q000235:genetics; D001692:Biological Transport; D015500:Chloramphenicol O-Acetyltransferase; D010450:Endopeptidases / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase