InterPro domain: IPR006214

Bax inhibitor-1 (BI-1) [ 1 ] is a suppressor of apoptosis that interacts with BCL2 and BCL-X. Human Bax BI-1 is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments predominantly localised to intracellular membranes. It has 6-7 membrane-spanning domains. The C termini of the mammalian BI-1 proteins are comprised of basic amino acids resembling some nuclear targeting sequences, but otherwise the predicted proteins lack motifs that suggest this function. As plant BI-1 appears to localise predominantly to the ER, it was suggested that plant BI-1 could also regulate cell death triggered by ER stress [ 2 ]. BI-1 appears to exert its effect through an interaction with calmodulin [ 3 ]. Crystal structure of a bacterial member reveals that these proteins mediate a calcium leak across the membrane in a pH-dependent manner. Calcium homoeostasis balances passive calcium leak with active calcium uptake. The structure exists in a pore-closed and pore-open conformation, at pHs of 8 and 6 respectively [ 4 ].

This entry represents BI-1 and related sequences, including lifeguard proteins, which also act as apoptotic regulators.

1. Identification of a novel conserved human gene, TEGT. Genomics 28, 301-4
2. Arabidopsis Bax inhibitor-1: A rheostat for ER stress-induced programmed cell death. Plant Signal Behav 3, 564-6
3. Bax inhibitor-1, a conserved cell death suppressor, is a key molecular switch downstream from a variety of biotic and abiotic stress signals in plants. Int J Mol Sci 10, 3149-67
4. Structural basis for a pH-sensitive calcium leak across membranes. Science 344, 1131-5