Alternative titles; symbols
HGNC Approved Gene Symbol: TMBIM6
Cytogenetic location: 12q13.12 Genomic coordinates (GRCh38): 12:49,741,557-49,764,934 (from NCBI)
TMBIM6 is an integral membrane protein that regulates cell death pathways controlled by BCL2 (151430) and BAX (600040) (Xu and Reed, 1998).
Walter et al. (1994) identified a single-copy gene in the rat for which 2 transcripts were found in each organ tested. The shorter transcript of about 1 kb was highly abundant in the postpubertal testis. The gene was therefore designated Tegt (for testis-enhanced gene transcript). Using a rat Tegt probe, Walter et al. (1995) screened a human testis cDNA library and isolated the human homolog of the rat Tegt gene. The gene in the rat and human did not belong to any known gene family of vertebrates. The deduced amino acid sequence of the gene and a bacterial protein of unknown function show low but significant homology and very similar hydrophobicity profiles. The 2 different transcripts are due to alternative usage of 2 polyadenylation sites. A nuclear targeting motif was present.
The mammalian proapoptotic protein BAX confers a lethal phenotype when expressed in yeast. By exploiting this phenotype, Xu and Reed (1998) identified a human BAX inhibitor, BI1. BI1 is an evolutionarily conserved integral membrane protein containing 6 predicted membrane-spanning segments and is predominantly localized to intracellular membranes, similar to BCL2 family proteins. The predicted protein contains 237 amino acids and is identical to TEGT.
Using hydrophobicity analysis, Carrara et al. (2012) determined that human BI1 has 6 transmembrane domains, with both the N and C termini in the cytosol.
Using in vivo crosslinking and coimmunoprecipitation studies, Xu and Reed (1998) demonstrated that BI1 can interact with BCL2 and BCLX(L) but not BAX or BAK, as demonstrated by in vivo crosslinking and coimmunoprecipitation studies. When overexpressed in mammalian cells, BI1 suppressed apoptosis induced by BAX, etoposide, staurosporine, and growth factor deprivation, but not by FAS (CD95; 134637). Conversely, BI1 antisense induced apoptosis. BI1 thus represents a regulator of cell death pathways controlled by BCL2 and BAX.
By Southern blot analysis of DNA from rat/human somatic cell hybrids, Walter et al. (1995) mapped the TEGT gene to human chromosome 12. Fluorescence in situ hybridization refined the assignment to 12q12-q13. This localization agrees with the assignment of the gene to rat chromosome 7 and to mouse chromosome 15.
Gross (2016) mapped the TMBIM6 gene to chromosome 12q13.12 based on an alignment of the TMBIM6 sequence (GenBank BC000916) with the genomic sequence (GRCh38).
Bailly-Maitre et al. (2006) found that Bi1-knockout mice subjected to hepatic ischemia-reperfusion (IR) injury showed increased histologic injury, increased apoptotic hepatocyte cell death, and higher activation of endoplasmic reticulum (ER) stress proteins compared to normal controls subjected to hepatic IR injury. Moreover, hepatic IR injury induced elevations in Bi1 mRNA in wildtype liver. Similar sensitization of kidney to ER stress and IR injury was observed in Bi1-null mice. The authors concluded that BI1 provides endogenous protection of liver and kidney from ER stress and IR injury.
Bailly-Maitre, B., Fondevila, C., Kaldas, F., Droin, N., Luciano, F., Ricci, J.-E., Croxton, R., Krajewska, M., Zapata, J. M., Kupiec-Weglinski, J. W., Farmer, D., Reed, J. C. Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. Proc. Nat. Acad. Sci. 103: 2809-2814, 2006. [PubMed: 16478805] [Full Text: https://doi.org/10.1073/pnas.0506854103]
Carrara, G., Saraiva, N., Gubser, C., Johnson, B. F., Smith, G. L. Six-transmembrane topology for Golgi anti-apoptotic protein (GAAP) and Bax inhibitor 1 (BI-1) provides model for the transmembrane Bax inhibitor-containing motif (TMBIM) family. J. Biol. Chem. 287: 15896-15905, 2012. [PubMed: 22418439] [Full Text: https://doi.org/10.1074/jbc.M111.336149]
Gross, M. B. Personal Communication. Baltimore, Md. 3/22/2016.
Walter, L., Dirks, B., Rothermel, E., Heyens, M., Szpirer, C., Levan, G., Gunther, E. A novel, conserved gene of the rat that is developmentally regulated in the testis. Mammalian Genome 5: 216-221, 1994. [PubMed: 8012111] [Full Text: https://doi.org/10.1007/BF00360548]
Walter, L., Marynen, P., Szpirer, J., Levan, G., Gunther, E. Identification of a novel conserved human gene, TEGT. Genomics 28: 301-304, 1995. [PubMed: 8530040] [Full Text: https://doi.org/10.1006/geno.1995.1145]
Xu, Q., Reed, J. C. Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. Molec. Cell 1: 337-346, 1998. [PubMed: 9660918] [Full Text: https://doi.org/10.1016/s1097-2765(00)80034-9]