After cleavage by MBTPS1, CREB3L3 in the Golgi membrane is cleaved by MBTPS2 (S2P) near the cytoplasmic face of the transmembrane domain (Bailey et al. 2007, inferred from mouse homologs in Zhang et al. 2006). By inference from cleavage of SREBFs (SREBPs), CREB3L3 is believed to be cleaved at approximately amino acid residue 323. The cleavage releases the N-terminal cytoplasmic domain into the cytosol.