Ku. Kalies et E. Hartmann, MEMBRANE TOPOLOGY OF THE 12- AND THE 25-KDA SUBUNITS OF THE MAMMALIANSIGNAL PEPTIDASE COMPLEX, The Journal of biological chemistry, 271(7), 1996, pp. 3925-3929
The cleavage of signal sequences of secretory and membrane proteins by
the signal peptidase complex occurs in the lumen of the endoplasmic r
eticulum. Mammalian signal peptidase consists of five subunits. Four h
ave been cloned, SPC18, SPC21, SPC22/23, and SPC25, of which all but S
PC25 have been demonstrated to be single-spanning membrane proteins ex
posed to the lumen of the endoplasmic reticulum. We have determined th
e cDNA sequence of the remaining 12-kDa subunit (SPC12) as well as the
membrane topologies of SPC12 and SPC25 in rough microsomes. Both poly
peptides span the membrane twice with their N and C termini facing the
cytosol and contain only very small, if any, lumenal domains. Therefo
re, SPC12 and SPC25 are likely to be involved in processes other than
the enzymatic cleavage of the signal sequence.