Catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein, resulting in the release of the fragment from the ER membrane into the cytoplasm. Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides . May be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein . Involved in the intramembrane cleavage of the integral membrane protein PSEN1 . Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner . May play a role in graft rejection (By similarity).
Endoplasmic reticulum membrane ; Multi-pass membrane protein . Membrane ; Multi-pass membrane protein ; Lumenal side .; [Isoform 4]: Cell membrane ; Multi-pass membrane protein .
Widely expressed with highest levels in kidney, liver, placenta, lung, leukocytes and small intestine and reduced expression in heart and skeletal muscle. Expressed abundantly in the CNS with highest levels in thalamus and medulla.
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