Transmembrane BAX inhibitor motif-containing protein 6 (TMBIM6)

Transmembrane BAX inhibitor motif-containing protein 6 (TMBIM6, also known as Bax inhibitor 1 or BI-1) is an evolutionarily conserved, highly hydrophobic integral membrane protein predominantly localized to the endoplasmic reticulum. TMBIM6 is the founding member of the TMBIM protein family, characterized by six to seven transmembrane domains and a unique C-terminal motif. Acting as an anti-apoptotic gatekeeper, TMBIM6 regulates cell survival under various stress conditions by modulating ER calcium content, suppressing ER stress responses, reducing oxidative stress, and limiting pro-apoptotic signaling. TMBIM6 is expressed in many tissues including liver, kidney, skeletal muscle, and brain. It plays vital roles in cellular homeostasis and adaptation to stress, but its upregulation is frequently observed in tumors, promoting cancer cell survival, progression, and drug resistance. Targeting TMBIM6 is under active preclinical investigation as a therapeutic strategy for diseases such as cancer, though no approved drugs currently target TMBIM6 directly.

Other names

Bax inhibitor 1BI-1TEGTBAXI1Testis-enhanced gene transcript proteinTransmembrane BAX inhibitor motif-containing protein 6

Antagonists (e.g., BIA): Bind TMBIM6, block its interaction with mTORC2, reduce mTORC2 activity and intracellular Ca²⁺ leak, thereby suppressing tumor cell survival and growth. Agonists (e.g., MQT): Induce conformational change in TMBIM6, increasing cytosolic Ca²⁺ and ROS, activating paraptotic (non-apoptotic) cell death specifically in cancer cells.