InterPro domain: IPR009542

This family represents the signal peptidase complex subunit 12kDa subunit (SPC12 or SPCS1) and its homologues, such as Spc1 from budding yeasts. The signal peptidase complex cleaves the signal sequence from proteins targeted to the endoplasmic reticulum (ER). Mammalian signal peptidase is as a complex of five different polypeptide chains [ 1 ], while the budding yeast SPC comprises four proteins [ 2 ]. Budding yeast Spc1 has been shown to be a nonessential component of the signal peptidase complex [ 3 ]. However, the Drosophila spase12 (yeast Spc1 homologue) null alleles are embryonic lethal [ 4 ].

Interestingly, human SPC12 has been linked to post-translational processing of proteins involved in virion assembly and secretion from flaviviruses [ 5 , 6 , 7 ].

Translocation of polypeptide chains across the endoplasmic reticulum (ER) membrane is triggered by signal sequences. Subsequently, signal recognition particle interacts with its membrane receptor and the ribosome-bound nascent chain is targeted to the ER where it is transferred into a protein-conducting channel. At some point, a second signal sequence recognition event takes place in the membrane and translocation of the nascent chain through the membrane occurs. The signal sequence of most secretory and membrane proteins is cleaved off at this stage. Cleavage occurs by the signal peptidase complex (SPC) as soon as the lumenal domain of the translocating polypeptide is large enough to expose its cleavage site to the enzyme. The signal peptidase complex is possibly also involved in proteolytic events in the ER membrane other than the processing of the signal sequence, for example the further digestion of the cleaved signal peptide or the degradation of membrane proteins [ 8 ].

1. Membrane topology of the 12- and the 25-kDa subunits of the mammalian signal peptidase complex. J. Biol. Chem. 271, 3925-9
2. The homologue of mammalian SPC12 is important for efficient signal peptidase activity in Saccharomyces cerevisiae. J. Biol. Chem. 271, 16460-5
3. Structurally related Spc1p and Spc2p of yeast signal peptidase complex are functionally distinct. J. Biol. Chem. 271, e60908
4. Drosophila signal peptidase complex member Spase12 is required for development and cell differentiation. PLoS ONE 8
5. Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS2. PLoS Pathog. 9, e1003589
6. A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature 535, 164-8
7. Host Factor SPCS1 Regulates the Replication of Japanese Encephalitis Virus through Interactions with Transmembrane Domains of NS2B. J. Virol. 92, 29094-9