SBH1 encodes the beta subunit of the heterotrimeric Sec61 complex, also referred to as the translocon (1, reviewed in 6). The Sec61 complex forms a channel in the endoplasmic reticulum (ER) membrane and mediates translocation of secretory and membrane proteins into the ER and also retrograde transport of misfolded proteins to the cytoplasm for degradation (reviewed in 7 and 6). The other subunits of the Sec61 complex are Sec61p, a 10-transmembrane domain protein that is the major translocon subunit, and Sss1p, a small essential protein thought to stabilize the complex (8, 9, 10).

Proteins that are transported into or across the ER membrane are directed there by signal sequences or by transmembrane segments that interact with the translocation apparatus. In S. cerevisiae the Sec61 complex mediates both co- and posttranslational translocation (while the mammalian Sec61 complex functions primarily with the cotranslational pathway; 11). During cotranslational translocation, ribosomes synthesizing signal sequence-containing proteins are targeted to the translocon via the signal recognition particle (SRP), and the ribosomes bind directly to Sec61p such that protein biosynthesis and translocation are synchronous (12). Posttranslational translocation requires Sec62p, Sec63p, Sec66p, and Sec72p (comprising the Sec63 complex), as well as Kar2p, in place of SRP to facilitate interaction of the full-length polypeptide with the translocon via the signal sequence (13, 1).

Retrograde transport of misfolded proteins into the cytoplasm (also called dislocation) employs the Sec61 channel via interaction with the 19S proteasome regulatory particle (14). This interaction, which competes with the ribosome-Sec61p interaction, defines the Sec61 complex as the principal proteasome receptor in the ER membrane (14).

Sbh1p is a small protein with a single C-terminal transmembrane domain, and an N-terminal cytosolic region that has guanine nucleotide exchange factor (GEF) activity (2, 15). In contrast to the inviability conferred by null mutations in either SEC61 or SSS1, sbh1 null mutations do not cause a growth defect (16, 17, 18), and an sbh1 sbh2 double null mutant exhibits temperature (heat)-sensitive growth (18). Expression of the 25-amino acid transmembrane domain alone rescues the ts growth defect of the double null mutant, and this domain is sufficient for interaction with Sec61p and Sss1p to form the Sec61 complex (5).

Physical interactions between Sbh1p and components of the exocyst complex, the oligosaccharyltransferase complex, and the signal peptidase complex have been reported (19, 20, 3, 5). Sbh1p is conserved among organisms; it is termed Sec61 beta in mammals, SecG in eubacteria, and Secbeta in archaea (reviewed in 21).

Last updated: 2007-11-09