elongated, “kidney bean”-like molecular shape that consists of 16 α-helices (A1–A16) and lacks β-sheets. The central helices A3-A14 form the armadillo (ARM)-like repeats (ARM1-ARM4), which are named after those found in β-catenin. Each ARM repeat is composed of three α-helices that pack into a superhelix. A crystal structure of yeast Sil1p complexed with the ADP-bound NBD of Kar2p/BiP revealed that the ARM domain of Sil1p wraps around lobe IIb of BiP’s NBD and makes additional contacts with lobe Ib. This interaction causes lobes Ib and IIb to rotate away from each other, leading to ADP release. Point mutations in the Sil1p-interacting site of Kar2p’s NBD specifically disrupted Sil1p binding but retained Kar2p’s ability to interact with Lhs1/GRP170, the other ER NEF, providing the first indication that their mechanisms of NEF activity were different. Homology mapping and comparisons with the structure of cytosolic HSPBP1 indicated that the region of SIL1 encoded by exons 6 and 9 constitutes major BiP-binding sites, and exon 10 encodes a minor interaction site. Tissue expression Although SIL1 is ubiquitously expressed, levels vary widely by tissue. The Human Protein Atlas (www.proteinatlas.org) shows that the expression pattern of SIL1 mirrors that of BiP even more closely than that of GRP170, which is a known UPR target, as is BiP. Perhaps the different expression pattern for GRP170 is due to its dual function as a chaperone and a NEF for BiP. SIL1 expression at a single-cell level has also been determined in a number of tissues, which does not strictly correlate with the secretory capacity of the cell, and tissues displaying the highest relative levels of SIL1 are not necessarily those most affected by loss of its function. This might imply an additional function, which has been demonstrated for Sil1p, or an as yet undiscovered role of SIL1 in certain tissues. Understanding this reason for variation in tissue expression will require further studies. Interactions SIL1 has been shown to interact with Binding immunoglobulin protein. References Further reading External links GeneReviews/NCBI/NIH/UW entry on Marinesco-Sjögren Syndrome