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.^[1]

Homologues are found in a variety of Gram-negative and Gram-positive bacteria, yeast, fungi, plants, animals and viruses. The E. coli genome encodes three paralogues, YbhL, YbhM and YccA. Distant homologues found in Drosophilia melanogaster and the rat are the N-methyl-D-aspartate receptor-associated protein (NMDARAI) and the N-methyl-D-aspartate receptor glutamate binding chain, respectively. Two others are the rat neural membrane protein 35 and the Arabidopsis thaliana Bax inhibitor-1 (BI-1) protein capable of suppressing Bax-induced cell death in yeast.

One of these proteins, TEGT or the Bax Inhibitor-1 (TC# 1.A.14.1.1), has a C-terminal domain that forms a Ca²⁺-permeable channel.^[2] BI-1 is an ER-localized protein that protects against apoptosis and ER stress. BI-1 has been proposed to modulate ER Ca²⁺ homeostasis by acting as a Ca²⁺-leak channel. These proteins are distantly related to the ionotropic glutamate-binding protein of the N-methyl D-aspartate (NMDA) receptor of man. Homologues include a putative cold shock inducible protein and a SecY stabilizing protein.^[1]

Based on experimental determination of the BI-1 topology, Bultynck et al. proposes that its C-terminal α-helical 20 amino acid peptide catalyzes Ca²⁺ flux both in vivo and in vitro.^[2] The Ca²⁺-leak properties were conserved among animal, but not plant and yeast orthologs. By mutating one of the critical aspartate residues (D₂₁₃) in the proposed Ca²⁺-channel pore in full-length BI-1, D₂₁₃ proved to be essential for BI-1 dependent ER Ca²⁺-leak.

Chang et al. published crystal structures of a bacterial homolog, YetJ (TC# 1.A.14.2.3) at 1.9 Å resolution and characterized its calcium leak activity. Its seven-transmembrane-helix fold features two triple-helix sandwiches wrapped around a central C-terminal helix.^[3] Structures obtained in closed and open conformations are reversibly interconvertible by changes in the pH. A hydrogen-bonded perturbed pair of conserved aspartyl residues explains the pH dependence of this transition, and the pH regulates calcium influx in proteoliposomes. Homology models for human BI-1 provided insight into its cytoprotective activity.^[3]

The generalized reaction catalyzed by TEGT channels is:

cations (out) ⇌ cations (in)