Programmed cell-death involves a set of Bcl-2 family proteins, some of which inhibit apoptosis (Bcl-2 and Bcl-XL) and some of which promote it (Bax and Bak). Human Bax inhibitor, 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 a function. As plant BI-1 appears to localise predominantly to the ER, we hypothesised that plant BI-1 could also regulate cell death triggered by ER stress [[cite:PUB00053809]]. BI-1 appears to exert its effect through an interaction with calmodulin [[cite:PUB00053810]]. The budding yeast member of this family has been found unexpectedly to encode a BH3 domain-containing protein (Ybh3p) that regulates the mitochondrial pathway of apoptosis in a phylogenetically conserved manner [[cite:PUB00110294]]. Examination of the crystal structure of a bacterial member of this family shows that these proteins mediate a calcium leak across the membrane that is pH-dependent. 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, and the pore can be opened by intracrystalline transition; together these findings suggest that pH controls the conformational transition [[cite:PUB00095242]].
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"Testis-enhanced_gene_transfer_family","extract":"The testis-enhanced gene transcript (TEGT) family includes the testis-enhanced gene transcript proteins of mammals, which are expressed at high levels in the testis, the putative glutamate/aspartate binding proteins of plants and animals, the YccA protein of Escherichia coli and the YetJ protein of Bacillus subtilis. These proteins are about 200-250 residues in length and exhibit 7 TMSs.
","thumbnail":null}],"literature":{"PUB00053809":{"PMID":19704470,"ISBN":null,"volume":"3","issue":"8","year":2008,"title":"Arabidopsis Bax inhibitor-1: A rheostat for ER stress-induced programmed cell death.","URL":null,"raw_pages":"564-6","medline_journal":"Plant Signal Behav","ISO_journal":"Plant Signal Behav","authors":["Watanabe N","Lam E."],"DOI_URL":null},"PUB00110294":{"PMID":21673659,"ISBN":null,"volume":"30","issue":"14","year":2011,"title":"A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis.","URL":null,"raw_pages":"2779-92","medline_journal":"EMBO J","ISO_journal":"EMBO J","authors":["Buttner S","Ruli D","Vogtle FN","Galluzzi L","Moitzi B","Eisenberg T","Kepp O","Habernig L","Carmona-Gutierrez D","Rockenfeller P","Laun P","Breitenbach M","Khoury C","Frohlich KU","Rechberger G","Meisinger C","Kroemer G","Madeo F."],"DOI_URL":null},"PUB00053810":{"PMID":19742129,"ISBN":null,"volume":"10","issue":"7","year":2009,"title":"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.","URL":null,"raw_pages":"3149-67","medline_journal":"Int J Mol Sci","ISO_journal":"Int J Mol Sci","authors":["Watanabe N","Lam E."],"DOI_URL":"http://dx.doi.org/10.3390/ijms10073149"},"PUB00095242":{"PMID":24904158,"ISBN":null,"volume":"344","issue":"6188","year":2014,"title":"Structural basis for a pH-sensitive calcium leak across membranes.","URL":null,"raw_pages":"1131-5","medline_journal":"Science","ISO_journal":"Science","authors":["Chang Y","Bruni R","Kloss B","Assur Z","Kloppmann E","Rost B","Hendrickson WA","Liu Q."],"DOI_URL":null},"PUB00053811":{"PMID":14671021,"ISBN":null,"volume":"16","issue":"1","year":2004,"title":"Dissection of Arabidopsis Bax inhibitor-1 suppressing Bax-, hydrogen peroxide-, and salicylic acid-induced cell death.","URL":null,"raw_pages":"21-32","medline_journal":"Plant Cell","ISO_journal":"Plant Cell","authors":["Kawai-Yamada M","Ohori Y","Uchimiya H."],"DOI_URL":"http://dx.doi.org/10.1105/tpc.014613"}},"set_info":{"accession":"CL0453","name":"Apoptosis-Inhib"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":248,"interactions":0,"matches":28281,"pathways":0,"proteins":27980,"proteomes":13018,"sets":1,"structural_models":{"alphafold":21884},"structures":9,"taxa":23036},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":193,"alignment:full":18272},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"4pgr","name":"Crystal structure of YetJ from Bacillus Subtilis at pH 8"}}}