SPPL3

Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries. Acts like a sheddase by mediating the proteolytic release and secretion of active site-containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1. Catalyzes the intramembrane cleavage of the envelope glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy virus independent of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis. May also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130. Plays a role in the regulation of cellular glycosylation processes. Required to link T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner..

Function from UniProtKB (Q8TCT6), read 2026-09-23. CC BY 4.0.