title: Identification of signal peptide peptidase, a presenilin-type aspartic protease.
abstract: Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence-derived human lymphocyte antigen-E epitopes that are recognized by the immune system, and to process hepatitis C virus core protein. We have identified human SPP as a polytopic membrane protein with sequence motifs characteristic of the presenilin-type aspartic proteases. SPP and potential eukaryotic homologs may represent another family of aspartic proteases that promote intramembrane proteolysis to release biologically important peptides.
authors.affiliation: Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), ETH-Hoenggerberg, 8093 Zürich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weihofen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Binns
authors.forename: Marius K
authors.initials: MK
authors.lastname: Lemberg
authors.forename: Keith
authors.initials: K
authors.lastname: Ashman
authors.forename: Bruno
authors.initials: B
authors.lastname: Martoglio
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001389:Azirines / Q000138:chemical synthesis / Q000494:pharmacology; D001665:Binding Sites; D001710:Biotin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D003001:Cloning, Molecular; D017124:Conserved Sequence; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006031:Glycosylation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D053764:Presenilin-1; D053766:Presenilin-2; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D001389:Azirines; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D011480:Protease Inhibitors; D011994:Recombinant Proteins; C460084:TBL(4)K compound; D001710:Biotin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C460085:signal peptide peptidase; C509280:BACE1 protein, human