| Modification Notes |
The yeast KAR2 gene was isolated by complementation of a mutation that blocks nuclear fusion (1). The predicted KAR2 protein sequence is most structurally homologous to mammalian BiP/GRP78 (1). The endoplasmic reticulum (ER) of mammalian cells contains a protein BiP that is believed to assist in the folding of secretory and transmembrane proteins (2). In yeast, Kar2 function is required for translocation of soluble proteins into the ER at a stage beyond the initial nascent chain-membrane association (3). Deficiencies in Kar2 may cause generalized failure of protein folding in the ER, leading to pleiotropic effects on cellular metabolism (2). The unfolded protein response (UPR) is a signal transduction pathway induced by a variety of ER stresses and functions to maintain homeostasis of the cellular membrane in eukaryotes (4,5). Additionally, Kar2 directly regulates the UPR by the interaction the transmembrane protein kinase/ribonuclease, Ire1, which transmits a signal from the ER to the nucleus (4,5). |